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  • Articles  (447)
  • United States  (332)
  • Crystallography, X-Ray  (115)
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  • 1
    Publication Date: 2021-05-19
    Description: The anthropogenic affectation was evaluated on the coast N of the Gulf of Batabanó in May 2003 (corresponding to the provinces of Matanzas and Havana), in areas located in the line of the coast. The results were compared with the historical information of the sector. In the coast N and the Ensenada of the Broa, the parameters oxygen saturation, DBO5 and DQO showed characteristic high values of eutrofication. The biggest contribution in the Cianoficies was in the near coastal areas to sources of organic contamination. In the case of the nutrients they show specific data of mesothrofic waters with tendency to the eutrofization and the silts presented a high affectation for toxic metals. The area near to Guanímar is distinguished to present conditions of organic contamination that favor heterothrofic conditions, corroborated by a prevalence of the processes of mineralization of the organic matter over primary production and lows values of fitoplankton concentration. On the contrary, in the region of Surgidero of Batabanó, the processes of synthesis of organic matter prevail suggested by a high primary production, and concentration of fitoplankton, with low breathing levels and mineralization of the organic matter, that indicates that the system is behaving autothrofically. In a general way, this sector is very affected by the anthropogenic impact. The information obtained is of great importance for the development of the fishing and tourist industries in the area.
    Description: Published
    Keywords: Phytoplankton ; Water quality ; Primary production ; Chemistry ; Environmental monitoring ; Phytoplankton ; Water quality ; Primary production ; Chemistry ; Environmental monitoring
    Repository Name: AquaDocs
    Type: Proceedings Paper
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  • 2
    Publication Date: 2022-05-26
    Description: Originally issued as Reference No. 67-21
    Description: This supplement to Volume I of the Data File, Continental Margin, Atlantic Coast of the United States (Woods Hole Oceanographic Institution Ref. No. 66-8) consists of three parts: 1. Errata for Volume I, 2. New station and sample data added to the file, and 3. Miscellaneous tables of information pertaining to the file. The user is referred to Volume I for explanation of the headings and abbreviations used and for a discussion of the structure of the file.
    Description: Submitted to the U.S. Geological Survey under Contract No. 14-08-0001-8358.
    Keywords: Continental margins ; Oceanography ; United States
    Repository Name: Woods Hole Open Access Server
    Type: Technical Report
    Format: application/pdf
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  • 3
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Jun 12;453(7197):835. doi: 10.1038/453835a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548033" target="_blank"〉PubMed〈/a〉
    Keywords: Financing, Organized/economics/*organization & administration ; *National Institutes of Health (U.S.)/economics ; Peer Review, Research/*methods/*standards ; Research Personnel/economics/standards ; United States
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 May 1;453(7191):9. doi: 10.1038/453009a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18461710" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; Genetic Privacy/*legislation & jurisprudence ; Genetics, Medical/*legislation & jurisprudence ; Genomics/legislation & jurisprudence/trends ; Humans ; Individuality ; *Prejudice ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Feb 28;451(7182):1035. doi: 10.1038/4511035a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305502" target="_blank"〉PubMed〈/a〉
    Keywords: Financing, Organized/economics/*organization & administration ; National Institutes of Health (U.S.)/*economics/*organization & administration ; Peer Review, Research/*methods/trends ; Research Personnel ; United States
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Mar 6;452(7183):6-7. doi: 10.1038/452006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18322484" target="_blank"〉PubMed〈/a〉
    Keywords: Celecoxib ; Confidentiality/*legislation & jurisprudence ; *Drug Industry ; Humans ; *Isoxazoles/adverse effects/pharmacology ; Peer Review, Research/*legislation & jurisprudence ; Periodicals as Topic/*legislation & jurisprudence ; *Pyrazoles/adverse effects/pharmacology ; *Sulfonamides/adverse effects/pharmacology ; United States
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  • 7
    Publication Date: 2008-11-18
    Description: Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein, which are two of the acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q (refs 3 and 4). More recently, members of the pentraxin family were found to interact with cell-surface Fcgamma receptors (FcgammaR) and activate leukocyte-mediated phagocytosis. Here we describe the structural mechanism for pentraxin's binding to FcgammaR and its functional activation of FcgammaR-mediated phagocytosis and cytokine secretion. The complex structure between human SAP and FcgammaRIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1:1 stoichiometry between SAP and FcgammaRIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for FcgammaR isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for FcgammaR binding and the inhibition of immune-complex-mediated phagocytosis by soluble pentraxins. These results establish antibody-like functions for pentraxins in the FcgammaR pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688732/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Jinghua -- Marnell, Lorraine L -- Marjon, Kristopher D -- Mold, Carolyn -- Du Clos, Terry W -- Sun, Peter D -- R01 AI28358/AI/NIAID NIH HHS/ -- T32 AI007538/AI/NIAID NIH HHS/ -- Z01 AI000853-09/Intramural NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):989-92. doi: 10.1038/nature07468. Epub 2008 Nov 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19011614" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Binding, Competitive ; C-Reactive Protein/chemistry/*immunology/*metabolism ; Crystallography, X-Ray ; Cytokines/immunology/secretion ; Humans ; Immunity, Innate/*immunology ; Immunoglobulin G/immunology/metabolism ; Macrophages/cytology/immunology ; Models, Molecular ; Phagocytosis ; Protein Conformation ; Receptors, IgG/chemistry/*immunology/*metabolism ; Serum Amyloid P-Component/chemistry/*immunology/*metabolism
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  • 8
    Publication Date: 2008-11-28
    Description: Gibberellins (GAs) are phytohormones essential for many developmental processes in plants. A nuclear GA receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1), has a primary structure similar to that of the hormone-sensitive lipases (HSLs). Here we analyse the crystal structure of Oryza sativa GID1 (OsGID1) bound with GA(4) and GA(3) at 1.9 A resolution. The overall structure of both complexes shows an alpha/beta-hydrolase fold similar to that of HSLs except for an amino-terminal lid. The GA-binding pocket corresponds to the substrate-binding site of HSLs. On the basis of the OsGID1 structure, we mutagenized important residues for GA binding and examined their binding activities. Almost all of them showed very little or no activity, confirming that the residues revealed by structural analysis are important for GA binding. The replacement of Ile 133 with Leu or Val-residues corresponding to those of the lycophyte Selaginella moellendorffii GID1s-caused an increase in the binding affinity for GA(34), a 2beta-hydroxylated GA(4). These observations indicate that GID1 originated from HSL and was further modified to have higher affinity and more strict selectivity for bioactive GAs by adapting the amino acids involved in GA binding in the course of plant evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimada, Asako -- Ueguchi-Tanaka, Miyako -- Nakatsu, Toru -- Nakajima, Masatoshi -- Naoe, Youichi -- Ohmiya, Hiroko -- Kato, Hiroaki -- Matsuoka, Makoto -- England -- Nature. 2008 Nov 27;456(7221):520-3. doi: 10.1038/nature07546.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioscience and Biotechnology Center, Nagoya University, Nagoya, Aichi 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19037316" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; Gibberellins/*chemistry/*metabolism ; Hydrolases/chemistry/metabolism ; Hydroxylation ; Models, Molecular ; Oryza/*chemistry/genetics/metabolism ; Plant Growth Regulators/*chemistry/*metabolism ; Plant Proteins/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Conformation ; Substrate Specificity ; Two-Hybrid System Techniques
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):282. doi: 10.1038/456282a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020565" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Federal Government ; Humans ; Leadership ; National Institutes of Health (U.S.)/*organization & administration ; *Stem Cells/cytology ; United States
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  • 10
    Publication Date: 2008-05-16
    Description: The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 (ref. 7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Patrick J -- Haire, Lesley F -- Lin, Yi Pu -- Liu, Junfeng -- Russell, Rupert J -- Walker, Philip A -- Skehel, John J -- Martin, Stephen R -- Hay, Alan J -- Gamblin, Steven J -- MC_U117512711/Medical Research Council/United Kingdom -- MC_U117512723/Medical Research Council/United Kingdom -- MC_U117570592/Medical Research Council/United Kingdom -- MC_U117584222/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 Jun 26;453(7199):1258-61. doi: 10.1038/nature06956. Epub 2008 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480754" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; *Drug Resistance, Viral ; Enzyme Inhibitors/chemistry/metabolism/pharmacology ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology/genetics ; Influenza A Virus, H5N1 Subtype/*drug effects/*enzymology/genetics ; Influenza, Human/virology ; Kinetics ; Models, Molecular ; Molecular Conformation ; Mutation/*genetics ; Neuraminidase/antagonists & inhibitors/*chemistry/*genetics/metabolism ; Oseltamivir/chemistry/metabolism/*pharmacology ; Protein Binding ; Zanamivir/pharmacology
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  • 11
    Publication Date: 2008-09-02
    Description: Translation initiation, the rate-limiting step of the universal process of protein synthesis, proceeds through sequential, tightly regulated steps. In bacteria, the correct messenger RNA start site and the reading frame are selected when, with the help of initiation factors IF1, IF2 and IF3, the initiation codon is decoded in the peptidyl site of the 30S ribosomal subunit by the fMet-tRNA(fMet) anticodon. This yields a 30S initiation complex (30SIC) that is an intermediate in the formation of the 70S initiation complex (70SIC) that occurs on joining of the 50S ribosomal subunit to the 30SIC and release of the initiation factors. The localization of IF2 in the 30SIC has proved to be difficult so far using biochemical approaches, but could now be addressed using cryo-electron microscopy and advanced particle separation techniques on the basis of three-dimensional statistical analysis. Here we report the direct visualization of a 30SIC containing mRNA, fMet-tRNA(fMet) and initiation factors IF1 and GTP-bound IF2. We demonstrate that the fMet-tRNA(fMet) is held in a characteristic and precise position and conformation by two interactions that contribute to the formation of a stable complex: one involves the transfer RNA decoding stem which is buried in the 30S peptidyl site, and the other occurs between the carboxy-terminal domain of IF2 and the tRNA acceptor end. The structure provides insights into the mechanism of 70SIC assembly and rationalizes the rapid activation of GTP hydrolysis triggered on 30SIC-50S joining by showing that the GTP-binding domain of IF2 would directly face the GTPase-activated centre of the 50S subunit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simonetti, Angelita -- Marzi, Stefano -- Myasnikov, Alexander G -- Fabbretti, Attilio -- Yusupov, Marat -- Gualerzi, Claudio O -- Klaholz, Bruno P -- England -- Nature. 2008 Sep 18;455(7211):416-20. doi: 10.1038/nature07192. Epub 2008 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Genetics and of Molecular and Cellular Biology, Department of Structural Biology and Genomics, Illkirch F-67404, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18758445" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallography, X-Ray ; Guanosine Triphosphate/chemistry/metabolism ; Models, Molecular ; Multiprotein Complexes/*chemistry/genetics/metabolism/*ultrastructure ; *Peptide Chain Initiation, Translational ; Prokaryotic Initiation Factor-1/chemistry/genetics/metabolism/ultrastructure ; Prokaryotic Initiation Factor-2/chemistry/genetics/metabolism/ultrastructure ; Protein Conformation ; RNA, Messenger/chemistry/genetics/metabolism ; RNA, Transfer, Met/chemistry/genetics/metabolism/ultrastructure ; Ribosome Subunits/chemistry/metabolism/ultrastructure ; Ribosomes/chemistry/*metabolism/*ultrastructure ; Thermus thermophilus/*enzymology/genetics/*ultrastructure
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  • 12
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 6;456(7218):2. doi: 10.1038/456002a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987684" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Genetically Modified ; Biotechnology/legislation & jurisprudence ; Food, Genetically Modified/standards ; *Guidelines as Topic ; Humans ; *Legislation, Drug ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 13
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smaglik, Paul -- England -- Nature. 2008 Jun 5;453(7196):818-20. doi: 10.1038/nj7196-818a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18623624" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*organization & administration/trends ; Alabama ; Biomedical Research/trends ; Biotechnology/*manpower/*organization & administration/trends ; Employment/trends ; Entrepreneurship/trends ; Humans ; United States ; United States National Aeronautics and Space Administration/*trends ; Universities/manpower
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  • 14
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-31
    Description: An experiment by the Gates Foundation is food for thought for other research agencies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Oct 30;455(7217):1150. doi: 10.1038/4551150a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971970" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics ; Creativity ; Foundations/*economics ; Humans ; Investments ; National Institutes of Health (U.S.)/economics ; Peer Review, Research/*standards ; Research Support as Topic/*economics ; *Risk-Taking ; United States
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  • 15
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-31
    Description: The values of scientific enquiry, rather than any particular policy positions on science, suggest a preference for one US presidential candidate over the other.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Oct 30;455(7217):1149. doi: 10.1038/4551149a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971969" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; *Politics ; *Science/standards ; United States
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  • 16
    Publication Date: 2008-12-19
    Description: Here we report on a 3.0 A crystal structure of a ternary complex of wild-type Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-nucleotide guide DNA and a 20-nucleotide target RNA containing cleavage-preventing mismatches at the 10-11 step. The seed segment (positions 2 to 8) adopts an A-helical-like Watson-Crick paired duplex, with both ends of the guide strand anchored in the complex. An arginine, inserted between guide-strand bases 10 and 11 in the binary complex, locking it in an inactive conformation, is released on ternary complex formation. The nucleic-acid-binding channel between the PAZ- and PIWI-containing lobes of argonaute widens on formation of a more open ternary complex. The relationship of structure to function was established by determining cleavage activity of ternary complexes containing position-dependent base mismatch, bulge and 2'-O-methyl modifications. Consistent with the geometry of the ternary complex, bulges residing in the seed segments of the target, but not the guide strand, were better accommodated and their complexes were catalytically active.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765400/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yanli -- Juranek, Stefan -- Li, Haitao -- Sheng, Gang -- Tuschl, Thomas -- Patel, Dinshaw J -- R01 AI068776/AI/NIAID NIH HHS/ -- R01 AI068776-02/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):921-6. doi: 10.1038/nature07666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial-Sloan Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092929" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics/*metabolism ; Base Pair Mismatch ; Base Pairing ; Base Sequence ; Crystallography, X-Ray ; DNA/chemistry/genetics/*metabolism ; Methylation ; Models, Molecular ; Phosphorylation ; Protein Conformation ; RNA/chemistry/genetics/*metabolism ; RNA Interference ; RNA-Induced Silencing Complex/*chemistry/genetics/*metabolism ; Substrate Specificity ; Thermus thermophilus/*chemistry
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  • 17
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Oct 16;455(7215):848. doi: 10.1038/455848a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Green Fluorescent Proteins/genetics/*metabolism ; Luminescence ; Mice ; *Nobel Prize ; *Research Personnel ; Swine ; United States
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  • 18
    Publication Date: 2008-08-30
    Description: The slicer activity of the RNA-induced silencing complex is associated with argonaute, the RNase H-like PIWI domain of which catalyses guide-strand-mediated sequence-specific cleavage of target messenger RNA. Here we report on the crystal structure of Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-base DNA guide strand, thereby identifying the nucleic-acid-binding channel positioned between the PAZ- and PIWI-containing lobes, as well as the pivot-like conformational changes associated with complex formation. The bound guide strand is anchored at both of its ends, with the solvent-exposed Watson-Crick edges of stacked bases 2 to 6 positioned for nucleation with the mRNA target, whereas two critically positioned arginines lock bases 10 and 11 at the cleavage site into an unanticipated orthogonal alignment. Biochemical studies indicate that key amino acid residues at the active site and those lining the 5'-phosphate-binding pocket made up of the Mid domain are critical for cleavage activity, whereas alterations of residues lining the 2-nucleotide 3'-end-binding pocket made up of the PAZ domain show little effect.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689319/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689319/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yanli -- Sheng, Gang -- Juranek, Stefan -- Tuschl, Thomas -- Patel, Dinshaw J -- P30 CA008748/CA/NCI NIH HHS/ -- R01 AI068776/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Nov 13;456(7219):209-13. doi: 10.1038/nature07315. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754009" target="_blank"〉PubMed〈/a〉
    Keywords: Aptamers, Nucleotide/metabolism ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; *Gene Silencing ; Hydrogen Bonding ; *Models, Molecular ; Mutation ; Protein Structure, Tertiary ; RNA/metabolism ; Thermus thermophilus/*chemistry/genetics
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  • 19
    Publication Date: 2008-09-02
    Description: A common hallmark of human cancers is the overexpression of telomerase, a ribonucleoprotein complex that is responsible for maintaining the length and integrity of chromosome ends. Telomere length deregulation and telomerase activation is an early, and perhaps necessary, step in cancer cell evolution. Here we present the high-resolution structure of the Tribolium castaneum catalytic subunit of telomerase, TERT. The protein consists of three highly conserved domains, organized into a ring-like structure that shares common features with retroviral reverse transcriptases, viral RNA polymerases and B-family DNA polymerases. Domain organization places motifs implicated in substrate binding and catalysis in the interior of the ring, which can accommodate seven to eight bases of double-stranded nucleic acid. Modelling of an RNA-DNA heteroduplex in the interior of this ring demonstrates a perfect fit between the protein and the nucleic acid substrate, and positions the 3'-end of the DNA primer at the active site of the enzyme, providing evidence for the formation of an active telomerase elongation complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gillis, Andrew J -- Schuller, Anthony P -- Skordalakes, Emmanuel -- England -- Nature. 2008 Oct 2;455(7213):633-7. doi: 10.1038/nature07283. Epub 2008 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18758444" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Binding Sites ; Catalysis ; Catalytic Domain ; Conserved Sequence ; Crystallization ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Nucleotides/metabolism ; Protein Structure, Tertiary ; Telomerase/*chemistry/metabolism ; Tribolium/*enzymology
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  • 20
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maher, Brendan -- England -- Nature. 2008 Jun 12;453(7197):828-9. doi: 10.1038/453828a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548027" target="_blank"〉PubMed〈/a〉
    Keywords: Embryonic Stem Cells/*cytology ; Female ; Humans ; Oocyte Donation/*economics/ethics/*legislation & jurisprudence/statistics & ; numerical data ; Ovum/cytology ; *Research Embryo Creation/economics/ethics/legislation & jurisprudence ; *State Government ; United States
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  • 21
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Courtland, Rachel -- England -- Nature. 2008 May 22;453(7194):432-3. doi: 10.1038/453432a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497777" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arctic Regions ; Conservation of Natural Resources/*legislation & jurisprudence/trends ; *Greenhouse Effect ; *Ice Cover ; Internationality ; Population Density ; Time Factors ; United States ; Ursidae/*physiology
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  • 22
    Publication Date: 2008-07-03
    Description: G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 A resolution crystal structure of a beta(1)-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane alpha-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the beta(1)-adrenergic receptor and binding of carazolol to the beta(2)-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the beta(2)-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923055/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923055/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warne, Tony -- Serrano-Vega, Maria J -- Baker, Jillian G -- Moukhametzianov, Rouslan -- Edwards, Patricia C -- Henderson, Richard -- Leslie, Andrew G W -- Tate, Christopher G -- Schertler, Gebhard F X -- MC_U105178937/Medical Research Council/United Kingdom -- MC_U105184322/Medical Research Council/United Kingdom -- MC_U105184325/Medical Research Council/United Kingdom -- MC_U105197215/Medical Research Council/United Kingdom -- U.1051.04.020(78937)/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Jul 24;454(7203):486-91. doi: 10.1038/nature07101. Epub 2008 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18594507" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-1 Receptor Agonists ; Adrenergic beta-1 Receptor Antagonists ; Adrenergic beta-Antagonists/chemistry/metabolism ; Amino Acid Motifs ; Animals ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; Ligands ; Models, Molecular ; Mutant Proteins/chemistry/genetics/metabolism ; Mutation ; Pindolol/analogs & derivatives/chemistry/metabolism ; Propanolamines/chemistry/metabolism ; Protein Conformation ; Receptors, Adrenergic, beta-1/*chemistry/metabolism ; Thermodynamics ; Turkeys
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wassarman, Paul M -- England -- Nature. 2008 Dec 4;456(7222):586-7. doi: 10.1038/456586a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Crystallography, X-Ray ; Egg Proteins/*chemistry/genetics/*metabolism ; Female ; Fertilization/physiology ; Male ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; Mice ; Ovum/*chemistry/*metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Spermatozoa/metabolism
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  • 24
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Courtland, Rachel -- England -- Nature. 2008 Jan 31;451(7178):508. doi: 10.1038/451508a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235463" target="_blank"〉PubMed〈/a〉
    Keywords: Environmental Monitoring/instrumentation/*legislation & jurisprudence ; *Law Enforcement ; New York City ; Police/*legislation & jurisprudence ; Security Measures/legislation & jurisprudence ; Terrorism/prevention & control ; Time Factors ; United States ; United States Department of Homeland Security/legislation & jurisprudence
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  • 25
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Oct 2;455(7213):565-6. doi: 10.1038/455565b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833222" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Leadership ; National Institutes of Health (U.S.)/ethics/*organization & ; administration/*trends ; United States
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  • 26
    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinberger, Sharon -- England -- Nature. 2008 Oct 2;455(7213):583-5. doi: 10.1038/455583a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833247" target="_blank"〉PubMed〈/a〉
    Keywords: Afghanistan ; Anthropology ; Iraq ; Military Science/*methods ; Social Sciences/*trends ; United States
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Oct 2;455(7213):565. doi: 10.1038/455565a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833221" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Energy Resources/economics/*trends ; Economics/*trends ; *Federal Government ; Greenhouse Effect ; Technology/economics/*trends ; United States
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Nov 6;456(7218):16. doi: 10.1038/456016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987708" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Energy Resources/economics/legislation & jurisprudence/trends ; *Federal Government ; Humans ; Leadership ; National Institutes of Health (U.S.)/economics ; Research Personnel/economics/psychology ; Research Support as Topic/*economics/legislation & jurisprudence/trends ; Science/*economics/legislation & jurisprudence/trends ; United States ; United States National Aeronautics and Space Administration/economics
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Sep 25;455(7212):431. doi: 10.1038/455431a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818598" target="_blank"〉PubMed〈/a〉
    Keywords: Embryonic Stem Cells ; *Federal Government ; Greenhouse Effect ; Humans ; *Politics ; Religion and Science ; Research Support as Topic ; Science/*economics/trends ; United States
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2008-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinberger, Sharon -- England -- Nature. 2008 Jan 24;451(7177):390-3. doi: 10.1038/451390a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216826" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bionics/trends ; History, 20th Century ; History, 21st Century ; Humans ; Internet ; Research/history/*trends ; Robotics/trends ; Security Measures/history/organization & administration/*trends ; Technology/history/*trends ; Terrorism/prevention & control ; United States ; United States Government Agencies/economics/history/organization & ; administration/*trends
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  • 31
    Publication Date: 2008-05-27
    Description: Understanding the energetics of molecular interactions is fundamental to all of the central quests of structural biology including structure prediction and design, mapping evolutionary pathways, learning how mutations cause disease, drug design, and relating structure to function. Hydrogen-bonding is widely regarded as an important force in a membrane environment because of the low dielectric constant of membranes and a lack of competition from water. Indeed, polar residue substitutions are the most common disease-causing mutations in membrane proteins. Because of limited structural information and technical challenges, however, there have been few quantitative tests of hydrogen-bond strength in the context of large membrane proteins. Here we show, by using a double-mutant cycle analysis, that the average contribution of eight interhelical side-chain hydrogen-bonding interactions throughout bacteriorhodopsin is only 0.6 kcal mol(-1). In agreement with these experiments, we find that 4% of polar atoms in the non-polar core regions of membrane proteins have no hydrogen-bond partner and the lengths of buried hydrogen bonds in soluble proteins and membrane protein transmembrane regions are statistically identical. Our results indicate that most hydrogen-bond interactions in membrane proteins are only modestly stabilizing. Weak hydrogen-bonding should be reflected in considerations of membrane protein folding, dynamics, design, evolution and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734483/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734483/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joh, Nathan Hyunjoong -- Min, Andrew -- Faham, Salem -- Whitelegge, Julian P -- Yang, Duan -- Woods, Virgil L -- Bowie, James U -- R01 CA081000/CA/NCI NIH HHS/ -- R01 CA081000-07/CA/NCI NIH HHS/ -- R01 CA081000-08/CA/NCI NIH HHS/ -- R01 CA081000-09/CA/NCI NIH HHS/ -- R01 GM063919/GM/NIGMS NIH HHS/ -- R01 GM063919-06/GM/NIGMS NIH HHS/ -- R01 GM063919-07/GM/NIGMS NIH HHS/ -- R01 GM063919-08/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jun 26;453(7199):1266-70. doi: 10.1038/nature06977. Epub 2008 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18500332" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriorhodopsins/chemistry/genetics/metabolism ; Crystallography, X-Ray ; Deuterium Exchange Measurement ; Hydrogen Bonding ; Membrane Proteins/*chemistry/genetics/*metabolism ; Models, Molecular ; Mutation/genetics ; Protein Folding ; Solubility ; Thermodynamics
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  • 32
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Sep 18;455(7211):273. doi: 10.1038/455273b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800096" target="_blank"〉PubMed〈/a〉
    Keywords: Competitive Behavior ; *Creativity ; *Federal Government ; Leadership ; United States
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  • 33
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Sep 25;455(7212):453. doi: 10.1038/455453a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818626" target="_blank"〉PubMed〈/a〉
    Keywords: Confidentiality ; *Federal Government ; Science/*organization & administration/trends ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Sep 4;455(7209):15. doi: 10.1038/455015a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉House Committee on Science. partyofone@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18769410" target="_blank"〉PubMed〈/a〉
    Keywords: Ecosystem ; *Environmental Monitoring/economics ; *Federal Government ; *Politics ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Aug 7;454(7205):680. doi: 10.1038/454680a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉House Committee on Science. partyofonecolumn@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18685673" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets/*legislation & jurisprudence/*trends ; *Federal Government ; *Politics ; Research Support as Topic/economics/*legislation & jurisprudence ; Science/*economics/legislation & jurisprudence ; Time Factors ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Jul 3;454(7200):16. doi: 10.1038/454016a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University's Center for the Environment, USA. partyofonecolumn@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596778" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Natural Resources/economics/legislation & jurisprudence ; *Federal Government ; Hydrogen-Ion Concentration ; *Lobbying ; Oceans and Seas ; Policy Making ; Seawater/*chemistry ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Jun 12;453(7197):838. doi: 10.1038/453838a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University's Center for the Environment, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548041" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; *Federal Government ; Humans ; National Institutes of Health (U.S.)/*economics ; Technology Transfer ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2008 May 22;453(7194):442-4. doi: 10.1038/453442a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497791" target="_blank"〉PubMed〈/a〉
    Keywords: Crime/*legislation & jurisprudence ; Criminal Law/*methods/standards ; DNA Fingerprinting ; Evaluation Studies as Topic ; Great Britain ; Humans ; Police ; Reproducibility of Results ; *Research ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Apr 3;452(7187):519. doi: 10.1038/452519a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University's Center for the Environment. partyofonecolumn@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18385707" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollution/analysis/*legislation & jurisprudence/prevention & control ; *Federal Government ; Humans ; Ozone/analysis/toxicity ; Plants/drug effects ; Smog/analysis/prevention & control ; Time Factors ; Uncertainty ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence
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  • 40
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wenner, Melinda -- England -- Nature. 2008 May 15;453(7193):271-3. doi: 10.1038/453271a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480787" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; Caspases/metabolism ; History, 20th Century ; History, 21st Century ; Humans ; Immunity, Innate ; Kenya ; Neoplasms/pathology/therapy ; Signal Transduction ; Ubiquitin/metabolism ; United States
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Feb 7;451(7179):621. doi: 10.1038/451621a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256639" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets/trends ; *Federal Government ; National Institutes of Health (U.S.)/economics ; *Persuasive Communication ; *Politics ; *Science/economics ; United States
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  • 42
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    Nature Publishing Group (NPG)
    Publication Date: 2008-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldston, David -- England -- Nature. 2008 Jan 24;451(7177):387. doi: 10.1038/451387a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216824" target="_blank"〉PubMed〈/a〉
    Keywords: *Budgets/trends ; *Federal Government ; Lobbying ; Politics ; Research/*economics ; Research Support as Topic/*economics ; United States
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  • 43
    Publication Date: 2008-01-04
    Description: Typical 2-Cys peroxiredoxins (Prxs) have an important role in regulating hydrogen peroxide-mediated cell signalling. In this process, Prxs can become inactivated through the hyperoxidation of an active site Cys residue to Cys sulphinic acid. The unique repair of this moiety by sulphiredoxin (Srx) restores peroxidase activity and terminates the signal. The hyperoxidized form of Prx exists as a stable decameric structure with each active site buried. Therefore, it is unclear how Srx can access the sulphinic acid moiety. Here we present the 2.6 A crystal structure of the human Srx-PrxI complex. This complex reveals the complete unfolding of the carboxy terminus of Prx, and its unexpected packing onto the backside of Srx away from the Srx active site. Binding studies and activity analyses of site-directed mutants at this interface show that the interaction is required for repair to occur. Moreover, rearrangements in the Prx active site lead to a juxtaposition of the Prx Gly-Gly-Leu-Gly and Srx ATP-binding motifs, providing a structural basis for the first step of the catalytic mechanism. The results also suggest that the observed interactions may represent a common mode for other proteins to bind to Prxs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646140/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646140/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jonsson, Thomas J -- Johnson, Lynnette C -- Lowther, W Todd -- R01 GM072866/GM/NIGMS NIH HHS/ -- R01 GM072866-03/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jan 3;451(7174):98-101. doi: 10.1038/nature06415.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Structural Biology and Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172504" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites/genetics ; Catalysis ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Multiprotein Complexes/chemistry/genetics/metabolism ; Mutagenesis, Site-Directed ; Oxidation-Reduction ; Oxidoreductases/*chemistry/genetics/*metabolism ; Oxidoreductases Acting on Sulfur Group Donors ; Peroxiredoxins/*chemistry/genetics/*metabolism ; Protein Structure, Quaternary ; Structure-Activity Relationship
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  • 44
    Publication Date: 2008-02-22
    Description: Messenger-RNA-directed protein synthesis is accomplished by the ribosome. In eubacteria, this complex process is initiated by a specialized transfer RNA charged with formylmethionine (tRNA(fMet)). The amino-terminal formylated methionine of all bacterial nascent polypeptides blocks the reactive amino group to prevent unfavourable side-reactions and to enhance the efficiency of translation initiation. The first enzymatic factor that processes nascent chains is peptide deformylase (PDF); it removes this formyl group as polypeptides emerge from the ribosomal tunnel and before the newly synthesized proteins can adopt their native fold, which may bury the N terminus. Next, the N-terminal methionine is excised by methionine aminopeptidase. Bacterial PDFs are metalloproteases sharing a conserved N-terminal catalytic domain. All Gram-negative bacteria, including Escherichia coli, possess class-1 PDFs characterized by a carboxy-terminal alpha-helical extension. Studies focusing on PDF as a target for antibacterial drugs have not revealed the mechanism of its co-translational mode of action despite indications in early work that it co-purifies with ribosomes. Here we provide biochemical evidence that E. coli PDF interacts directly with the ribosome via its C-terminal extension. Crystallographic analysis of the complex between the ribosome-interacting helix of PDF and the ribosome at 3.7 A resolution reveals that the enzyme orients its active site towards the ribosomal tunnel exit for efficient co-translational processing of emerging nascent chains. Furthermore, we have found that the interaction of PDF with the ribosome enhances cell viability. These results provide the structural basis for understanding the coupling between protein synthesis and enzymatic processing of nascent chains, and offer insights into the interplay of PDF with the ribosome-associated chaperone trigger factor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bingel-Erlenmeyer, Rouven -- Kohler, Rebecca -- Kramer, Gunter -- Sandikci, Arzu -- Antolic, Snjezana -- Maier, Timm -- Schaffitzel, Christiane -- Wiedmann, Brigitte -- Bukau, Bernd -- Ban, Nenad -- England -- Nature. 2008 Mar 6;452(7183):108-11. doi: 10.1038/nature06683. Epub 2008 Feb 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288106" target="_blank"〉PubMed〈/a〉
    Keywords: Amidohydrolases/*chemistry/deficiency/genetics/*metabolism ; Amino Acid Sequence ; Arabinose/metabolism ; Binding Sites ; Crystallography, X-Ray ; Escherichia coli/*enzymology/genetics/growth & development/metabolism ; Genetic Complementation Test ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; N-Formylmethionine/metabolism ; Peptidylprolyl Isomerase/metabolism ; Protein Binding ; *Protein Biosynthesis ; *Protein Processing, Post-Translational ; Protein Structure, Secondary ; RNA, Transfer, Met/genetics/metabolism ; Ribosome Subunits/chemistry/metabolism ; Ribosomes/*chemistry/*metabolism
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  • 45
    Publication Date: 2008-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whisstock, James C -- Bottomley, Stephen P -- England -- Nature. 2008 Oct 30;455(7217):1189-90. doi: 10.1038/4551189a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18972012" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/chemistry/metabolism ; Animals ; Antithrombin III/*chemistry/*metabolism ; Biopolymers/chemistry/metabolism ; Crystallography, X-Ray ; Dimerization ; Humans ; Models, Molecular ; Protein Conformation ; Protein Folding
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  • 46
    Publication Date: 2008-07-04
    Description: Neurotrophins (NTs) are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. NTs bind to two distinct classes of glycosylated receptor: the p75 neurotrophin receptor (p75(NTR)) and tyrosine kinase receptors (Trks). Whereas p75(NTR) binds to all NTs, the Trk subtypes are specific for each NT. The question of whether NTs stimulate p75(NTR) by inducing receptor homodimerization is still under debate. Here we report the 2.6-A resolution crystal structure of neurotrophin-3 (NT-3) complexed to the ectodomain of glycosylated p75(NTR). In contrast to the previously reported asymmetric complex structure, which contains a dimer of nerve growth factor (NGF) bound to a single ectodomain of deglycosylated p75(NTR) (ref. 3), we show that NT-3 forms a central homodimer around which two glycosylated p75(NTR) molecules bind symmetrically. Symmetrical binding occurs along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster. A comparison of the symmetrical and asymmetric structures reveals significant differences in ligand-receptor interactions and p75(NTR) conformations. Biochemical experiments indicate that both NT-3 and NGF bind to p75(NTR) with 2:2 stoichiometry in solution, whereas the 2:1 complexes are the result of artificial deglycosylation. We therefore propose that the symmetrical 2:2 complex reflects a native state of p75(NTR) activation at the cell surface. These results provide a model for NTs-p75(NTR) recognition and signal generation, as well as insights into coordination between p75(NTR) and Trks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Yong -- Cao, Peng -- Yu, Hong-jun -- Jiang, Tao -- England -- Nature. 2008 Aug 7;454(7205):789-93. doi: 10.1038/nature07089. Epub 2008 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596692" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Crystallography, X-Ray ; Dimerization ; Glycosylation ; Humans ; Ligands ; Models, Molecular ; Neurotrophin 3/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Rats ; Receptor, Nerve Growth Factor/*chemistry/genetics/*metabolism ; Spodoptera
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Aug 28;454(7208):1029. doi: 10.1038/4541029a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756202" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conservation of Natural Resources/*legislation & jurisprudence/trends ; Ecology/*legislation & jurisprudence/methods ; Ecosystem ; *Federal Government ; United States ; United States Government Agencies/legislation & jurisprudence
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Aug 21;454(7207):917. doi: 10.1038/454917a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719537" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax ; Bioterrorism/*legislation & jurisprudence ; Forensic Sciences/*standards ; Law Enforcement/*ethics ; Research Personnel/*legislation & jurisprudence ; Suicide ; United States ; United States Government Agencies/legislation & jurisprudence
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2008 Sep 18;455(7211):269. doi: 10.1038/455269b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800093" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Humans ; Internationality ; Japan ; Mice ; Patents as Topic/*legislation & jurisprudence ; *Pluripotent Stem Cells/cytology ; Time Factors ; United States ; Universities
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  • 50
    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2008 Jun 19;453(7198):962-3. doi: 10.1038/453962a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563108" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryonic Stem Cells/cytology ; Humans ; Japan ; Mice ; *Patents as Topic/legislation & jurisprudence ; *Pluripotent Stem Cells/cytology ; United States
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  • 51
    Publication Date: 2008-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maseland, Robbert -- England -- Nature. 2008 Sep 11;455(7210):167. doi: 10.1038/455167c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784701" target="_blank"〉PubMed〈/a〉
    Keywords: Competitive Behavior ; Creativity ; Europe ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Internationality ; Science/history/*standards/trends ; United States
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  • 52
    Publication Date: 2008-04-25
    Description: Bacteriophage lambda has for many years been a model system for understanding mechanisms of gene regulation. A 'genetic switch' enables the phage to transition from lysogenic growth to lytic development when triggered by specific environmental conditions. The key component of the switch is the cI repressor, which binds to two sets of three operator sites on the lambda chromosome that are separated by about 2,400 base pairs (bp). A hallmark of the lambda system is the pairwise cooperativity of repressor binding. In the absence of detailed structural information, it has been difficult to understand fully how repressor molecules establish the cooperativity complex. Here we present the X-ray crystal structure of the intact lambda cI repressor dimer bound to a DNA operator site. The structure of the repressor, determined by multiple isomorphous replacement methods, reveals an unusual overall architecture that allows it to adopt a conformation that appears to facilitate pairwise cooperative binding to adjacent operator sites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stayrook, Steven -- Jaru-Ampornpan, Peera -- Ni, Jenny -- Hochschild, Ann -- Lewis, Mitchell -- R01 GM044025/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Apr 24;452(7190):1022-5. doi: 10.1038/nature06831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton Walk, Philadelphia, Pennsylvania 19102-6059, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18432246" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Bacteriophage lambda/*chemistry/genetics ; Crystallography, X-Ray ; DNA-Binding Proteins/*chemistry/*metabolism ; Dimerization ; Models, Biological ; *Models, Molecular ; Operator Regions, Genetic/*genetics ; Protein Conformation ; Repressor Proteins/*chemistry/*metabolism ; Structure-Activity Relationship ; Viral Regulatory and Accessory Proteins/*chemistry/*metabolism
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    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blobel, Gunter -- England -- Nature. 2008 Nov 6;456(7218):52. doi: 10.1038/456052a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gunter Blobel is at the Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. blobel@mail.rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987733" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Physiological Phenomena ; History, 20th Century ; Microscopy, Electron/history ; Organelles/ultrastructure ; Romania ; United States
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  • 54
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blumberg, Baruch S -- England -- Nature. 2008 Mar 27;452(7186):422. doi: 10.1038/452422a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baruch S. Blumberg is at the Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497, USA.baruch.blumberg@fccc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368111" target="_blank"〉PubMed〈/a〉
    Keywords: Exobiology/history ; History, 20th Century ; Humans ; Molecular Biology/*history ; Nobel Prize ; Plasmids/genetics/history ; Transduction, Genetic/history ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jul 24;454(7203):381. doi: 10.1038/454381e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650879" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Acquired Immunodeficiency Syndrome/*economics ; Biomedical Research/*economics ; *Federal Government ; Humans ; Research Support as Topic ; United States
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  • 56
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jul 24;454(7203):368. doi: 10.1038/454368a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650857" target="_blank"〉PubMed〈/a〉
    Keywords: *Environmental Monitoring ; *Federal Government ; *Greenhouse Effect ; United States
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2008 Nov 13;456(7219):146-7. doi: 10.1038/456146a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19005517" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; *Greenhouse Effect ; *Policy Making ; United States
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jul 10;454(7201):138. doi: 10.1038/454138a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615027" target="_blank"〉PubMed〈/a〉
    Keywords: Afghanistan ; Culture ; Iraq ; Military Personnel/education ; Military Science/*methods ; *Social Sciences ; United States ; Warfare
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2008 Oct 16;455(7215):858-60. doi: 10.1038/455858a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923486" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archaeology/legislation & jurisprudence ; Dinosaurs ; *Fossils ; Humans ; *Indians, North American/education ; Paleontology/education/*legislation & jurisprudence/manpower ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 60
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2008 Sep 25;455(7212):442-5. doi: 10.1038/455442a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryo Research ; *Federal Government ; Greenhouse Effect ; Humans ; Science/economics/*organization & administration/trends ; Space Flight/trends ; Stem Cells ; Technology/economics/*organization & administration/trends ; United States
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  • 61
    Publication Date: 2008-02-01
    Description: The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889492/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stouffer, Amanda L -- Acharya, Rudresh -- Salom, David -- Levine, Anna S -- Di Costanzo, Luigi -- Soto, Cinque S -- Tereshko, Valentina -- Nanda, Vikas -- Stayrook, Steven -- DeGrado, William F -- R37 GM054616/GM/NIGMS NIH HHS/ -- T32 GM008275/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jan 31;451(7178):596-9. doi: 10.1038/nature06528.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235504" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/chemistry/metabolism/pharmacology ; Crystallography, X-Ray ; Drug Resistance, Viral/genetics ; Histidine/metabolism ; Hydrogen-Ion Concentration ; Influenza A virus/*chemistry/genetics/metabolism ; Ion Channel Gating/drug effects ; Models, Molecular ; Protein Structure, Quaternary ; Protons ; Structure-Activity Relationship ; Tryptophan/metabolism ; Viral Matrix Proteins/*antagonists & inhibitors/*chemistry/genetics/metabolism
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  • 62
    Publication Date: 2008-02-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2008 Feb 21;451(7181):875. doi: 10.1038/451875a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288150" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; Lobbying ; *Research Personnel ; Science/*organization & administration ; United States
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  • 63
    Publication Date: 2008-11-07
    Description: The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains-a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker-is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-A-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798118/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798118/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bornholdt, Zachary A -- Prasad, B V Venkataram -- AI36040/AI/NIAID NIH HHS/ -- R37 AI036040/AI/NIAID NIH HHS/ -- R37 AI036040-21/AI/NIAID NIH HHS/ -- RR002250/RR/NCRR NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):985-8. doi: 10.1038/nature07444. Epub 2008 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987632" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Humans ; Influenza A Virus, H5N1 Subtype/*chemistry/*pathogenicity ; Influenza, Human/epidemiology/virology ; Models, Molecular ; Protein Multimerization ; Protein Structure, Tertiary ; Vietnam/epidemiology ; Viral Nonstructural Proteins/*chemistry/ultrastructure ; Virulence ; Virulence Factors
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  • 64
    Publication Date: 2008-09-17
    Description: Hedgehog (Hh) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration-dependent cellular differentiation or proliferation responses. Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signalling has been implicated in human birth defects and cancer. Hh signalling is mediated by its amino-terminal domain (HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle. Reception of the HhN signal is modulated by several cell-surface proteins on responding cells, including Patched (Ptc), Smoothened (Smo), Ihog (known as CDO or CDON in mammals) and the vertebrate-specific proteins Hip (also known as Hhip) and Gas1 (ref. 11). Drosophila Ihog and its vertebrate homologues CDO and BOC contain multiple immunoglobulin and fibronectin type III (FNIII) repeats, and the first FNIII repeat of Ihog binds Drosophila HhN in a heparin-dependent manner. Surprisingly, pull-down experiments suggest that a mammalian Sonic hedgehog N-terminal domain (ShhN) binds a non-orthologous FNIII repeat of CDO. Here we report biochemical, biophysical and X-ray structural studies of a complex between ShhN and the third FNIII repeat of CDO. We show that the ShhN-CDO interaction is completely unlike the HhN-Ihog interaction and requires calcium, which binds at a previously undetected site on ShhN. This site is conserved in nearly all Hh proteins and is a hotspot for mediating interactions between ShhN and CDO, Ptc, Hip and Gas1. Mutations in vertebrate Hh proteins causing holoprosencephaly and brachydactyly type A1 map to this calcium-binding site and disrupt interactions with these partners.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679680/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679680/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLellan, Jason S -- Zheng, Xiaoyan -- Hauk, Glenn -- Ghirlando, Rodolfo -- Beachy, Philip A -- Leahy, Daniel J -- R01 HD055545/HD/NICHD NIH HHS/ -- Z99 DK999999/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 16;455(7215):979-83. doi: 10.1038/nature07358. Epub 2008 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18794898" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Calcium/metabolism ; Cell Adhesion Molecules/chemistry/metabolism ; Cell Cycle Proteins/chemistry/metabolism ; Cell Line ; *Conserved Sequence ; Crystallography, X-Ray ; Drosophila Proteins/*chemistry/*metabolism ; Drosophila melanogaster/chemistry ; Fibronectins/chemistry ; GPI-Linked Proteins ; Hedgehog Proteins/*chemistry/genetics/*metabolism ; Humans ; Immunoglobulin G/chemistry/metabolism ; Membrane Glycoproteins/*chemistry/*metabolism ; Membrane Proteins/chemistry/metabolism ; Mice ; Models, Molecular ; Protein Binding/genetics ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/*metabolism ; *Sequence Homology, Amino Acid ; Signal Transduction ; Tumor Suppressor Proteins/chemistry/metabolism
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  • 65
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2008 Mar 13;452(7184):146. doi: 10.1038/452146a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337794" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/*economics ; Consultants/statistics & numerical data ; *Faculty ; Human Growth Hormone/economics ; Humans ; Patents as Topic/*statistics & numerical data ; Research Personnel/economics ; *Technology Transfer ; United States ; Universities/*economics/manpower
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redner, Sid -- England -- Nature. 2008 May 1;453(7191):47-8. doi: 10.1038/453047a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451851" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Friends ; Internet ; *Models, Biological ; *Probability ; Protein Binding ; Saccharomyces cerevisiae/metabolism ; Schools ; Sensitivity and Specificity ; Social Behavior ; United States
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2008 Apr 17;452(7189):806-8. doi: 10.1038/452806a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18431826" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Animals ; Body Size ; Bone and Bones/*anatomy & histology ; Diet/history ; Dwarfism ; *Fossils ; *Geography ; History, Ancient ; Hominidae/*anatomy & histology/*classification ; Humans ; *Motion Pictures as Topic ; Palau ; United States
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  • 68
    Publication Date: 2008-11-07
    Description: Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet-induced DNA damage, and resulting in a strong predisposition to develop skin cancers. The use of rare cutting DNA endonucleases-such as homing endonucleases, also known as meganucleases-constitutes one possible strategy for repairing DNA lesions. Homing endonucleases have emerged as highly specific molecular scalpels that recognize and cleave DNA sites, promoting efficient homologous gene targeting through double-strand-break-induced homologous recombination. Here we describe two engineered heterodimeric derivatives of the homing endonuclease I-CreI, produced by a semi-rational approach. These two molecules-Amel3-Amel4 and Ini3-Ini4-cleave DNA from the human XPC gene (xeroderma pigmentosum group C), in vitro and in vivo. Crystal structures of the I-CreI variants complexed with intact and cleaved XPC target DNA suggest that the mechanism of DNA recognition and cleavage by the engineered homing endonucleases is similar to that of the wild-type I-CreI. Furthermore, these derivatives induced high levels of specific gene targeting in mammalian cells while displaying no obvious genotoxicity. Thus, homing endonucleases can be designed to recognize and cleave the DNA sequences of specific genes, opening up new possibilities for genome engineering and gene therapy in xeroderma pigmentosum patients whose illness can be treated ex vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redondo, Pilar -- Prieto, Jesus -- Munoz, Ines G -- Alibes, Andreu -- Stricher, Francois -- Serrano, Luis -- Cabaniols, Jean-Pierre -- Daboussi, Fayza -- Arnould, Sylvain -- Perez, Christophe -- Duchateau, Philippe -- Paques, Frederic -- Blanco, Francisco J -- Montoya, Guillermo -- England -- Nature. 2008 Nov 6;456(7218):107-11. doi: 10.1038/nature07343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Macromolecular Crystallography Group, Spanish National Cancer Research Centre (CNIO), c/Melchor Fdez. Almagro 3, 28029 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987743" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Cell Line ; Cricetinae ; Cricetulus ; Crystallography, X-Ray ; DNA/chemistry/*genetics/*metabolism ; DNA Repair ; DNA Restriction Enzymes/*chemistry/genetics/*metabolism/toxicity ; DNA-Binding Proteins/*genetics ; Enzyme Stability ; *Genetic Engineering ; Humans ; Models, Molecular ; Phosphorylation ; Protein Multimerization ; Substrate Specificity ; Xeroderma Pigmentosum/*genetics
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  • 69
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    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2008 Jan 31;451(7178):510. doi: 10.1038/451510a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235465" target="_blank"〉PubMed〈/a〉
    Keywords: Alligators and Crocodiles/classification ; Animals ; *Classification ; Dinosaurs/classification ; *Fossils ; Museums ; Paleontology/ethics/*standards ; Poland ; Reptiles/*classification ; *Scientific Misconduct ; *Terminology as Topic ; United States
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  • 70
    Publication Date: 2008-07-29
    Description: Epac proteins are activated by binding of the second messenger cAMP and then act as guanine nucleotide exchange factors for Rap proteins. The Epac proteins are involved in the regulation of cell adhesion and insulin secretion. Here we have determined the structure of Epac2 in complex with a cAMP analogue (Sp-cAMPS) and RAP1B by X-ray crystallography and single particle electron microscopy. The structure represents the cAMP activated state of the Epac2 protein with the RAP1B protein trapped in the course of the exchange reaction. Comparison with the inactive conformation reveals that cAMP binding causes conformational changes that allow the cyclic nucleotide binding domain to swing from a position blocking the Rap binding site towards a docking site at the Ras exchange motif domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rehmann, Holger -- Arias-Palomo, Ernesto -- Hadders, Michael A -- Schwede, Frank -- Llorca, Oscar -- Bos, Johannes L -- England -- Nature. 2008 Sep 4;455(7209):124-7. doi: 10.1038/nature07187. Epub 2008 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. h.rehmann@UMCutrecht.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18660803" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Binding Sites ; Carrier Proteins/*chemistry/*metabolism/ultrastructure ; Crystallography, X-Ray ; Cyclic AMP/*analogs & derivatives/chemistry/metabolism ; Enzyme Activation ; Guanine Nucleotide Exchange Factors/*chemistry/*metabolism/ultrastructure ; Humans ; Mice ; Microscopy, Electron ; Models, Molecular ; Protein Binding ; Protein Conformation ; Thionucleotides/*chemistry/*metabolism ; rap GTP-Binding Proteins/chemistry/*metabolism/ultrastructure
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  • 71
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    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dance, Amber -- England -- Nature. 2008 Aug 21;454(7207):928. doi: 10.1038/454928a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754132" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax ; Bacillus anthracis/classification/genetics ; Bioterrorism/*legislation & jurisprudence ; *Forensic Sciences/methods/standards ; Humans ; Peer Review ; *Publishing ; Research Personnel/*legislation & jurisprudence ; Suicide ; United States ; United States Government Agencies/*legislation & jurisprudence
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  • 72
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    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jun 12;453(7197):837. doi: 10.1038/453837c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548038" target="_blank"〉PubMed〈/a〉
    Keywords: Boston ; Containment of Biohazards/*standards ; Laboratories/economics/legislation & jurisprudence/*standards ; *National Institutes of Health (U.S.)/economics ; Risk Assessment ; United States
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  • 73
    Publication Date: 2008-03-07
    Description: Carbonic anhydrase, a zinc enzyme found in organisms from all kingdoms, catalyses the reversible hydration of carbon dioxide and is used for inorganic carbon acquisition by phytoplankton. In the oceans, where zinc is nearly depleted, diatoms use cadmium as a catalytic metal atom in cadmium carbonic anhydrase (CDCA). Here we report the crystal structures of CDCA in four distinct forms: cadmium-bound, zinc-bound, metal-free and acetate-bound. Despite lack of sequence homology, CDCA is a structural mimic of a functional beta-carbonic anhydrase dimer, with striking similarity in the spatial organization of the active site residues. CDCA readily exchanges cadmium and zinc at its active site--an apparently unique adaptation to oceanic life that is explained by a stable opening of the metal coordinating site in the absence of metal. Given the central role of diatoms in exporting carbon to the deep sea, their use of cadmium in an enzyme critical for carbon acquisition establishes a remarkable link between the global cycles of cadmium and carbon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Yan -- Feng, Liang -- Jeffrey, Philip D -- Shi, Yigong -- Morel, Francois M M -- England -- Nature. 2008 Mar 6;452(7183):56-61. doi: 10.1038/nature06636.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18322527" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/metabolism ; Binding Sites ; Cadmium/*metabolism ; Carbonic Anhydrases/*chemistry/*metabolism ; Catalysis ; Crystallography, X-Ray ; Diatoms/*enzymology ; Dimerization ; Kinetics ; Marine Biology ; Models, Molecular ; Molecular Mimicry ; Protein Structure, Secondary ; Seawater/*microbiology ; Zinc/*metabolism
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  • 74
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellgren, Ronald L -- England -- Nature. 2008 Nov 20;456(7220):337-8. doi: 10.1038/456337a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020611" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Calcium/metabolism ; Calcium-Binding Proteins/*chemistry/*metabolism ; Calpain/*antagonists & inhibitors/chemistry/*metabolism ; *Catalytic Domain ; Crystallography, X-Ray ; Models, Molecular ; Peptide Fragments/chemistry/metabolism ; Protein Binding ; Protein Multimerization ; Rats
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  • 75
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    Publication Date: 2008-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dance, Amber -- England -- Nature. 2008 Aug 7;454(7205):672. doi: 10.1038/454672a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18685659" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax/prevention & control ; Bioterrorism/*prevention & control ; Humans ; Male ; *Research Personnel/psychology/standards ; Security Measures/ethics/*legislation & jurisprudence ; *Suicide ; United States ; United States Government Agencies/*legislation & jurisprudence
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jun 5;453(7196):697. doi: 10.1038/453697a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18528339" target="_blank"〉PubMed〈/a〉
    Keywords: Genome, Human ; Genomics/*trends ; History, 20th Century ; History, 21st Century ; Human Genome Project/history ; Humans ; National Human Genome Research Institute (U.S.)/history/*organization & ; administration/trends ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 77
    Publication Date: 2008-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swazey, Judith P -- England -- Nature. 2008 Jul 31;454(7204):575; author reply 575. doi: 10.1038/454575a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18668084" target="_blank"〉PubMed〈/a〉
    Keywords: Data Collection/*methods ; National Institutes of Health (U.S.)/economics ; Research Design ; Scientific Misconduct/*statistics & numerical data ; United States
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  • 78
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jun 5;453(7196):697-8. doi: 10.1038/453697b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18528338" target="_blank"〉PubMed〈/a〉
    Keywords: Embryonic Stem Cells ; *Federal Government ; Greenhouse Effect ; Humans ; Nuclear Weapons/legislation & jurisprudence ; Science/*legislation & jurisprudence ; United States
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  • 79
    Publication Date: 2008-10-17
    Description: Repeating intermolecular protein association by means of beta-sheet expansion is the mechanism underlying a multitude of diseases including Alzheimer's, Huntington's and Parkinson's and the prion encephalopathies. A family of proteins, known as the serpins, also forms large stable multimers by ordered beta-sheet linkages leading to intracellular accretion and disease. These 'serpinopathies' include early-onset dementia caused by mutations in neuroserpin, liver cirrhosis and emphysema caused by mutations in alpha(1)-antitrypsin (alpha(1)AT), and thrombosis caused by mutations in antithrombin. Serpin structure and function are quite well understood, and the family has therefore become a model system for understanding the beta-sheet expansion disorders collectively known as the conformational diseases. To develop strategies to prevent and reverse these disorders, it is necessary to determine the structural basis of the intermolecular linkage and of the pathogenic monomeric state. Here we report the crystallographic structure of a stable serpin dimer which reveals a domain swap of more than 50 residues, including two long antiparallel beta-strands inserting in the centre of the principal beta-sheet of the neighbouring monomer. This structure explains the extreme stability of serpin polymers, the molecular basis of their rapid propagation, and provides critical new insights into the structural changes which initiate irreversible beta-sheet expansion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamasaki, Masayuki -- Li, Wei -- Johnson, Daniel J D -- Huntington, James A -- G0801899/Medical Research Council/United Kingdom -- England -- Nature. 2008 Oct 30;455(7217):1255-8. doi: 10.1038/nature07394. Epub 2008 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Cambridge, Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923394" target="_blank"〉PubMed〈/a〉
    Keywords: Antithrombin III/*chemistry/*metabolism ; Biopolymers/chemistry/metabolism ; Crystallography, X-Ray ; Dimerization ; Humans ; Models, Molecular ; Protein Conformation
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  • 80
    Publication Date: 2008-04-25
    Description: Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587245/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587245/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Cai-Guang -- Yi, Chengqi -- Duguid, Erica M -- Sullivan, Christopher T -- Jian, Xing -- Rice, Phoebe A -- He, Chuan -- GM071440/GM/NIGMS NIH HHS/ -- R01 GM071440/GM/NIGMS NIH HHS/ -- R01 GM071440-03/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Apr 24;452(7190):961-5. doi: 10.1038/nature06889.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18432238" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/analogs & derivatives/metabolism ; Binding Sites ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA Damage ; DNA Repair ; DNA Repair Enzymes/*chemistry/metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Dioxygenases/*chemistry/*metabolism ; Escherichia coli Proteins/*chemistry/*metabolism ; Humans ; Mixed Function Oxygenases/*chemistry/*metabolism ; Models, Molecular ; Protein Binding ; RNA/*metabolism
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  • 81
    Publication Date: 2008-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klagsbrun, Michael -- Moses, Marsha A -- England -- Nature. 2008 Feb 14;451(7180):781. doi: 10.1038/451781a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Children's Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. michael.klagsbrun@childrens.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18273010" target="_blank"〉PubMed〈/a〉
    Keywords: Angiogenesis Inhibitors/therapeutic use ; Awards and Prizes ; Biomarkers ; History, 20th Century ; History, 21st Century ; Humans ; Neoplasms/*blood supply/drug therapy ; *Neovascularization, Pathologic/drug therapy ; United States
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  • 82
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 May 22;453(7194):427-8. doi: 10.1038/453427b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497763" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/*ethics/*legislation & jurisprudence/standards ; Developing Countries ; *Helsinki Declaration ; Humans ; Infant ; International Cooperation ; Placebos ; United States ; United States Food and Drug Administration/ethics/*legislation & jurisprudence
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 May 15;453(7193):258. doi: 10.1038/453258a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; *Environmental Monitoring/legislation & jurisprudence ; Fertilizers/*adverse effects/toxicity ; Humans ; Sewage/*adverse effects/statistics & numerical data ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence
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  • 84
    Publication Date: 2008-05-27
    Description: Members of the epidermal growth factor receptor (EGFR) or ErbB/HER family and their activating ligands are essential regulators of diverse developmental processes. Inappropriate activation of these receptors is a key feature of many human cancers, and its reversal is an important clinical goal. A natural secreted antagonist of EGFR signalling, called Argos, was identified in Drosophila. We showed previously that Argos functions by directly binding (and sequestering) growth factor ligands that activate EGFR. Here we describe the 1.6-A resolution crystal structure of Argos bound to an EGFR ligand. Contrary to expectations, Argos contains no EGF-like domain. Instead, a trio of closely related domains (resembling a three-finger toxin fold) form a clamp-like structure around the bound EGF ligand. Although structurally unrelated to the receptor, Argos mimics EGFR by using a bipartite binding surface to entrap EGF. The individual Argos domains share unexpected structural similarities with the extracellular ligand-binding regions of transforming growth factor-beta family receptors. The three-domain clamp of Argos also resembles the urokinase-type plasminogen activator (uPA) receptor, which uses a similar mechanism to engulf the EGF-like module of uPA. Our results indicate that undiscovered mammalian counterparts of Argos may exist among other poorly characterized structural homologues. In addition, the structures presented here define requirements for the design of artificial EGF-sequestering proteins that would be valuable anti-cancer therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526102/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526102/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, Daryl E -- Stayrook, Steven E -- Shi, Fumin -- Narayan, Kartik -- Lemmon, Mark A -- R01 CA079992/CA/NCI NIH HHS/ -- R01 CA079992-10/CA/NCI NIH HHS/ -- R01 CA125432/CA/NCI NIH HHS/ -- R01 CA125432-01A1/CA/NCI NIH HHS/ -- England -- Nature. 2008 Jun 26;453(7199):1271-5. doi: 10.1038/nature06978. Epub 2008 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18500331" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Drosophila Proteins/*chemistry/*metabolism ; Drosophila melanogaster/*chemistry/cytology ; Epidermal Growth Factor/*chemistry/*metabolism ; Eye Proteins/*chemistry/*metabolism ; Humans ; Ligands ; Membrane Proteins/*chemistry/*metabolism ; Models, Molecular ; Nerve Tissue Proteins/*chemistry/*metabolism ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/chemistry/*metabolism ; Receptors, Transforming Growth Factor beta/chemistry/metabolism ; Spodoptera
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  • 85
    Publication Date: 2008-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robbins, Anthony -- England -- Nature. 2008 May 15;453(7193):281. doi: 10.1038/453281b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480792" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Great Britain ; *Health Education/history ; *Health Policy/history ; History, 20th Century ; Humans ; Pertussis Vaccine/administration & dosage/history ; *Public Opinion ; United States ; Vaccination/contraindications/history/*utilization
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  • 86
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, Ian M -- England -- Nature. 2008 Aug 28;454(7208):1049. doi: 10.1038/4541049a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756230" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Mobility ; Education, Graduate/statistics & numerical data/trends ; Research Personnel/education/*statistics & numerical data ; United States
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  • 87
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haigwood, Nancy -- England -- Nature. 2008 Aug 28;454(7208):1039. doi: 10.1038/4541039a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756221" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax ; Bioterrorism/*legislation & jurisprudence ; Postal Service ; Research Personnel/*psychology ; Suicide ; United States ; United States Government Agencies/*legislation & jurisprudence
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  • 88
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 May 8;453(7192):133-4. doi: 10.1038/453133b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464686" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets/legislation & jurisprudence ; *Competitive Behavior ; Engineering/economics/standards ; *Federal Government ; Physics/economics/standards ; Research/*economics/legislation & jurisprudence/*standards ; United States
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  • 89
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Christopher -- England -- Nature. 2008 Jan 31;451(7178):532-3. doi: 10.1038/451532a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235492" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/chemistry/metabolism/pharmacology ; Animals ; Crystallography, X-Ray ; Humans ; Hydrogen-Ion Concentration ; Influenza A virus/*chemistry/genetics/pathogenicity/physiology ; Ion Channel Gating/drug effects ; Nuclear Magnetic Resonance, Biomolecular ; Protein Structure, Quaternary ; Protons ; Viral Matrix Proteins/antagonists & inhibitors/*chemistry/metabolism
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  • 90
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Andrew -- England -- Nature. 2008 Jul 17;454(7202):290. doi: 10.1038/454290a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Andrew Brown is a writer on science and religion. laptop@thewormbook.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18633408" target="_blank"〉PubMed〈/a〉
    Keywords: Bahamas ; Fund Raising/*history ; History, 20th Century ; *Religion and Science ; United States
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  • 91
    Publication Date: 2008-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rogers Hollingsworth, J -- Muller, Karl H -- Hollingsworth, Ellen Jane -- England -- Nature. 2008 Jul 24;454(7203):412-3. doi: 10.1038/454412a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Wisconsin (Madison), 455 North Park Street, Madison, Wisconsin 53706, USA. hollingsjr@aol.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650902" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Europe ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Science/economics/*history/standards/*trends ; United States
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  • 92
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Apr 10;452(7188):666. doi: 10.1038/452666a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401360" target="_blank"〉PubMed〈/a〉
    Keywords: Genetic Predisposition to Disease/*genetics ; Genetic Testing/economics/standards/*trends ; Humans ; Internationality ; Registries ; Reproducibility of Results ; Sensitivity and Specificity ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 93
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brumfiel, Geoff -- England -- Nature. 2008 Oct 9;455(7214):712-3. doi: 10.1038/455712b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18843320" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; Fund Raising/*economics ; Housing/economics ; Internationality ; Research Support as Topic/*economics ; United States
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  • 94
    Publication Date: 2008-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeLisi, Charles -- England -- Nature. 2008 Oct 16;455(7215):876-7. doi: 10.1038/455876a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Boston University, USA. delisi@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923499" target="_blank"〉PubMed〈/a〉
    Keywords: Congresses as Topic/*history ; Environmental Pollution/adverse effects ; Genetic Predisposition to Disease ; Genetic Variation ; Genome, Human ; Genomics/economics/history ; History, 20th Century ; Human Genome Project/economics/*history ; Humans ; National Institutes of Health (U.S.)/history ; New Mexico ; Politics ; Sequence Analysis, DNA ; United States
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  • 95
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kowalczykowski, Stephen C -- R01 GM062653/GM/NIGMS NIH HHS/ -- R37 GM062653/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 May 22;453(7194):463-6. doi: 10.1038/453463a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497811" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; *DNA Repair ; Models, Molecular ; Molecular Conformation ; Rec A Recombinases/*chemistry/*metabolism ; *Recombination, Genetic/genetics ; *Sequence Homology, Nucleic Acid
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  • 96
    Publication Date: 2008-11-21
    Description: The Ca(2+)-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0 A structure of Ca(2+)-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca(2+), illustrating key residues in a peripheral domain that serve to stabilize the protease core on Ca(2+) binding. Fully activated calpain binds ten Ca(2+) atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847431/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moldoveanu, Tudor -- Gehring, Kalle -- Green, Douglas R -- P01 CA069381/CA/NCI NIH HHS/ -- P01 CA069381-140010/CA/NCI NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI040646/AI/NIAID NIH HHS/ -- R01 AI040646-14/AI/NIAID NIH HHS/ -- R01 AI044828/AI/NIAID NIH HHS/ -- R01 AI044828-12/AI/NIAID NIH HHS/ -- R01 AI047891/AI/NIAID NIH HHS/ -- R01 AI047891-12/AI/NIAID NIH HHS/ -- R37 GM052735/GM/NIGMS NIH HHS/ -- R37 GM052735-19/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Nov 20;456(7220):404-8. doi: 10.1038/nature07353.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020622" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Calcium/metabolism ; Calcium-Binding Proteins/*chemistry/genetics/*metabolism ; Calpain/antagonists & inhibitors/*chemistry/*metabolism ; *Catalytic Domain ; Crystallography, X-Ray ; EF Hand Motifs ; Enzyme Activation ; Protein Binding ; Protein Multimerization ; Protein Processing, Post-Translational ; Rats ; Structure-Activity Relationship ; Substrate Specificity
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2008-05-03
    Description: During infection by Gram-negative pathogenic bacteria, the type III secretion system (T3SS) is assembled to allow for the direct transmission of bacterial virulence effectors into the host cell. The T3SS system is characterized by a series of prominent multi-component rings in the inner and outer bacterial membranes, as well as a translocation pore in the host cell membrane. These are all connected by a series of polymerized tubes that act as the direct conduit for the T3SS proteins to pass through to the host cell. During assembly of the T3SS, as well as the evolutionarily related flagellar apparatus, a post-translational cleavage event within the inner membrane proteins EscU/FlhB is required to promote a secretion-competent state. These proteins have long been proposed to act as a part of a molecular switch, which would regulate the appropriate chronological secretion of the various T3SS apparatus components during assembly and subsequently the transported virulence effectors. Here we show that a surface type II beta-turn in the Escherichia coli protein EscU undergoes auto-cleavage by a mechanism involving cyclization of a strictly conserved asparagine residue. Structural and in vivo analysis of point and deletion mutations illustrates the subtle conformational effects of auto-cleavage in modulating the molecular features of a highly conserved surface region of EscU, a potential point of interaction with other T3SS components at the inner membrane. In addition, this work provides new structural insight into the distinct conformational requirements for a large class of self-cleaving reactions involving asparagine cyclization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zarivach, Raz -- Deng, Wanyin -- Vuckovic, Marija -- Felise, Heather B -- Nguyen, Hai V -- Miller, Samuel I -- Finlay, B Brett -- Strynadka, Natalie C J -- 5R01 AI030479/AI/NIAID NIH HHS/ -- R01 AI030479/AI/NIAID NIH HHS/ -- U54 AI057141/AI/NIAID NIH HHS/ -- England -- Nature. 2008 May 1;453(7191):124-7. doi: 10.1038/nature06832.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, and the Center for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451864" target="_blank"〉PubMed〈/a〉
    Keywords: Asparagine/chemistry/metabolism ; Circular Dichroism ; Crystallography, X-Ray ; Cyclization ; Enteropathogenic Escherichia coli/*chemistry/*metabolism/pathogenicity ; Escherichia coli Proteins/*chemistry/genetics/*metabolism ; Models, Chemical ; Models, Molecular ; Protein Structure, Tertiary ; Salmonella typhimurium/genetics/metabolism ; Virulence Factors/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Mar 20;452(7185):254. doi: 10.1038/452254a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354433" target="_blank"〉PubMed〈/a〉
    Keywords: Amputation ; Drug Industry/*legislation & jurisprudence ; Drug Labeling/*legislation & jurisprudence/*standards ; Female ; Humans ; Promethazine/administration & dosage/adverse effects ; Risk Assessment ; *Supreme Court Decisions ; United States ; United States Food and Drug Administration/legislation & jurisprudence/standards
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2008-12-05
    Description: Species-specific recognition between the egg extracellular matrix (zona pellucida) and sperm is the first, crucial step of mammalian fertilization. Zona pellucida filament components ZP3 and ZP2 act as sperm receptors, and mice lacking either of the corresponding genes produce oocytes without a zona pellucida and are completely infertile. Like their counterparts in the vitelline envelope of non-mammalian eggs and many other secreted eukaryotic proteins, zona pellucida subunits polymerize using a 'zona pellucida (ZP) domain' module, whose conserved amino-terminal part (ZP-N) was suggested to constitute a domain of its own. No atomic structure has been reported for ZP domain proteins, and there is no structural information on any conserved vertebrate protein that is essential for fertilization and directly involved in egg-sperm binding. Here we describe the 2.3 angstrom (A) resolution structure of the ZP-N fragment of mouse primary sperm receptor ZP3. The ZP-N fold defines a new immunoglobulin superfamily subtype with a beta-sheet extension characterized by an E' strand and an invariant tyrosine residue implicated in polymerization. The structure strongly supports the presence of ZP-N repeats within the N-terminal region of ZP2 and other vertebrate zona pellucida/vitelline envelope proteins, with implications for overall egg coat architecture, the post-fertilization block to polyspermy and speciation. Moreover, it provides an important framework for understanding human diseases caused by mutations in ZP domain proteins and developing new methods of non-hormonal contraception.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monne, Magnus -- Han, Ling -- Schwend, Thomas -- Burendahl, Sofia -- Jovine, Luca -- G0500367/Medical Research Council/United Kingdom -- England -- Nature. 2008 Dec 4;456(7222):653-7. doi: 10.1038/nature07599.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Karolinska Institutet, Department of Biosciences and Nutrition, Halsovagen 7, SE-141 57 Huddinge, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052627" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; CHO Cells ; Conserved Sequence ; Cricetinae ; Cricetulus ; Crystallization ; Crystallography, X-Ray ; Egg Proteins/*chemistry/genetics/*metabolism ; Female ; Male ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Ovum/*chemistry/*metabolism ; Peptide Fragments/chemistry/genetics/metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Repetitive Sequences, Amino Acid ; Spermatozoa/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2008-03-21
    Description: The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis. Here we describe the computational design of eight enzymes that use two different catalytic motifs to catalyse the Kemp elimination-a model reaction for proton transfer from carbon-with measured rate enhancements of up to 10(5) and multiple turnovers. Mutational analysis confirms that catalysis depends on the computationally designed active sites, and a high-resolution crystal structure suggests that the designs have close to atomic accuracy. Application of in vitro evolution to enhance the computational designs produced a 〉200-fold increase in k(cat)/K(m) (k(cat)/K(m) of 2,600 M(-1)s(-1) and k(cat)/k(uncat) of 〉10(6)). These results demonstrate the power of combining computational protein design with directed evolution for creating new enzymes, and we anticipate the creation of a wide range of useful new catalysts in the future.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothlisberger, Daniela -- Khersonsky, Olga -- Wollacott, Andrew M -- Jiang, Lin -- DeChancie, Jason -- Betker, Jamie -- Gallaher, Jasmine L -- Althoff, Eric A -- Zanghellini, Alexandre -- Dym, Orly -- Albeck, Shira -- Houk, Kendall N -- Tawfik, Dan S -- Baker, David -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 May 8;453(7192):190-5. doi: 10.1038/nature06879. Epub 2008 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354394" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Motifs ; Binding Sites/genetics ; Catalysis ; Computational Biology ; *Computer Simulation ; Crystallography, X-Ray ; Directed Molecular Evolution/*methods ; Drug Design ; Drug Evaluation, Preclinical ; Enzymes/*chemistry/genetics/*metabolism ; Kinetics ; Models, Chemical ; Models, Molecular ; Protein Engineering/*methods ; Quantum Theory ; Sensitivity and Specificity
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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