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  • Articles  (130)
  • Protein Conformation  (130)
  • 2005-2009  (72)
  • 2000-2004  (58)
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  • Articles  (130)
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  • 1
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    T cell activation by lipopeptide antigens (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-24
    Description: Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moody, D Branch -- Young, David C -- Cheng, Tan-Yun -- Rosat, Jean-Pierre -- Roura-Mir, Carme -- O'Connor, Peter B -- Zajonc, Dirk M -- Walz, Andrew -- Miller, Marvin J -- Levery, Steven B -- Wilson, Ian A -- Costello, Catherine E -- Brenner, Michael B -- AI30988/AI/NIAID NIH HHS/ -- AI50216/AI/NIAID NIH HHS/ -- AR48632/AR/NIAMS NIH HHS/ -- CA58896/CA/NCI NIH HHS/ -- GM25845/GM/NIGMS NIH HHS/ -- GM62116/GM/NIGMS NIH HHS/ -- P20 RR16459/RR/NCRR NIH HHS/ -- P41-RR10888/RR/NCRR NIH HHS/ -- S10-RR10493/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 23;303(5657):527-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Smith Building Room 514, 1 Jimmy Fund Way, Boston, MA 02115, USA. bmoody@rics.bwh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14739458" target="_blank"〉PubMed〈/a〉
    Keywords: *Antigen Presentation ; Antigens, Bacterial/chemistry/*immunology/metabolism ; Antigens, CD1/chemistry/immunology/metabolism ; Cell Line ; Chromatography, High Pressure Liquid ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Hydroxylation ; Lipoproteins/chemistry/*immunology/metabolism ; *Lymphocyte Activation ; Models, Molecular ; Mycobacterium tuberculosis/growth & development/*immunology ; Oxazoles/chemistry/*immunology/metabolism ; Protein Conformation ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocytes/*immunology ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-06-26
    Description: The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Outeiro, Tiago Fleming -- Kontopoulos, Eirene -- Altmann, Stephen M -- Kufareva, Irina -- Strathearn, Katherine E -- Amore, Allison M -- Volk, Catherine B -- Maxwell, Michele M -- Rochet, Jean-Christophe -- McLean, Pamela J -- Young, Anne B -- Abagyan, Ruben -- Feany, Mel B -- Hyman, Bradley T -- Kazantsev, Aleksey G -- 5P50-NS38372A-06/NS/NINDS NIH HHS/ -- R01-NS049221/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 27;317(5837):516-9. Epub 2007 Jun 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Alzheimer's Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17588900" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Animals, Genetically Modified ; Cell Death/drug effects ; Cell Line, Tumor ; Cells, Cultured ; Disease Models, Animal ; Dopamine/physiology ; Dose-Response Relationship, Drug ; Drosophila melanogaster ; Furans/*pharmacology ; Humans ; Models, Molecular ; Neurons/cytology/drug effects ; Parkinson Disease/*drug therapy/metabolism/pathology/*physiopathology ; Protein Conformation ; Quinolines/*pharmacology ; RNA, Small Interfering/genetics ; Rats ; Sirtuin 1 ; Sirtuin 2 ; Sirtuins/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Transfection ; Tubulin/metabolism ; alpha-Synuclein/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    The kinase domain of titin controls muscle gene expression and protein turnover (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-04-02
    Description: The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lange, Stephan -- Xiang, Fengqing -- Yakovenko, Andrey -- Vihola, Anna -- Hackman, Peter -- Rostkova, Elena -- Kristensen, Jakob -- Brandmeier, Birgit -- Franzen, Gereon -- Hedberg, Birgitta -- Gunnarsson, Lars Gunnar -- Hughes, Simon M -- Marchand, Sylvie -- Sejersen, Thomas -- Richard, Isabelle -- Edstrom, Lars -- Ehler, Elisabeth -- Udd, Bjarne -- Gautel, Mathias -- G0200496(63216)/Medical Research Council/United Kingdom -- G0300213/Medical Research Council/United Kingdom -- PG/03/049/15364/British Heart Foundation/United Kingdom -- New York, N.Y. -- Science. 2005 Jun 10;308(5728):1599-603. Epub 2005 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Muscle Signalling and Development, Randall Division, King's College London, London SE1 1UL, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15802564" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Catalytic Domain ; Cell Line ; Cell Nucleus/metabolism ; Connectin ; *Gene Expression Regulation ; Heat-Shock Proteins/metabolism ; Humans ; Ligands ; Mice ; Mice, Inbred C3H ; Molecular Sequence Data ; Muscle Proteins/*chemistry/genetics/*metabolism ; Muscle, Skeletal/*metabolism ; Muscular Diseases/genetics ; Mutation ; Myocytes, Cardiac/*metabolism ; Protein Binding ; Protein Conformation ; Protein Kinases/*chemistry/genetics/*metabolism ; Protein Structure, Tertiary ; Proteins/metabolism ; Rats ; Respiratory Insufficiency/genetics/metabolism ; Sarcomeres/metabolism ; Serum Response Factor/metabolism ; Signal Transduction ; Two-Hybrid System Techniques ; Ubiquitin-Protein Ligases/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Structure of human urokinase plasminogen activator in complex with its receptor (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-02-04
    Description: The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation. We report the crystal structure at 1.9 angstroms of the urokinase receptor complexed with the urokinase amino-terminal fragment and an antibody against the receptor. The three domains of urokinase receptor form a concave shape with a central cone-shaped cavity where the urokinase fragment inserts. The structure provides insight into the flexibility of the urokinase receptor that enables its interaction with a wide variety of ligands and a basis for the design of urokinase-urokinase receptor antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huai, Qing -- Mazar, Andrew P -- Kuo, Alice -- Parry, Graham C -- Shaw, David E -- Callahan, Jennifer -- Li, Yongdong -- Yuan, Cai -- Bian, Chuanbing -- Chen, Liqing -- Furie, Bruce -- Furie, Barbara C -- Cines, Douglas B -- Huang, Mingdong -- R01 HL086584/HL/NHLBI NIH HHS/ -- R01 HL086584-01/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2006 Feb 3;311(5761):656-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hemostasis and Thrombosis, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16456079" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/chemistry/metabolism ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Models, Molecular ; Peptide Fragments/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/immunology/metabolism ; Receptors, Urokinase Plasminogen Activator ; Urokinase-Type Plasminogen Activator/*chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Structure of a cofactor-deficient nitrogenase MoFe protein (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-04-16
    Description: One of the most complex biosynthetic processes in metallobiochemistry is the assembly of nitrogenase, the key enzyme in biological nitrogen fixation. We describe here the crystal structure of an iron-molybdenum cofactor-deficient form of the nitrogenase MoFe protein, into which the cofactor is inserted in the final step of MoFe protein assembly. The MoFe protein folds as a heterotetramer containing two copies each of the homologous alpha and beta subunits. In this structure, one of the three alpha subunit domains exhibits a substantially changed conformation, whereas the rest of the protein remains essentially unchanged. A predominantly positively charged funnel is revealed; this funnel is of sufficient size to accommodate insertion of the negatively charged cofactor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmid, Benedikt -- Ribbe, Markus W -- Einsle, Oliver -- Yoshida, Mika -- Thomas, Leonard M -- Dean, Dennis R -- Rees, Douglas C -- Burgess, Barbara K -- New York, N.Y. -- Science. 2002 Apr 12;296(5566):352-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, Mail Code 147-75CH, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11951047" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Azotobacter vinelandii/*enzymology ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; Dimerization ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Molybdoferredoxin/*chemistry/genetics/*metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Static Electricity ; Surface Properties
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Nitrogenase MoFe-protein at 1.16 A resolution: a central ligand in the FeMo-cofactor (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-09-07
    Description: A high-resolution crystallographic analysis of the nitrogenase MoFe-protein reveals a previously unrecognized ligand coordinated to six iron atoms in the center of the catalytically essential FeMo-cofactor. The electron density for this ligand is masked in structures with resolutions lower than 1.55 angstroms, owing to Fourier series termination ripples from the surrounding iron and sulfur atoms in the cofactor. The central atom completes an approximate tetrahedral coordination for the six iron atoms, instead of the trigonal coordination proposed on the basis of lower resolution structures. The crystallographic refinement at 1.16 angstrom resolution is consistent with this newly detected component being a light element, most plausibly nitrogen. The presence of a nitrogen atom in the cofactor would have important implications for the mechanism of dinitrogen reduction by nitrogenase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Einsle, Oliver -- Tezcan, F Akif -- Andrade, Susana L A -- Schmid, Benedikt -- Yoshida, Mika -- Howard, James B -- Rees, Douglas C -- New York, N.Y. -- Science. 2002 Sep 6;297(5587):1696-700.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 147-75CH, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215645" target="_blank"〉PubMed〈/a〉
    Keywords: Azotobacter vinelandii/enzymology ; Coenzymes/*chemistry/metabolism ; Crystallography, X-Ray ; Ligands ; Models, Molecular ; Molybdoferredoxin/*chemistry/metabolism ; Nitrogen/chemistry ; Nitrogenase/*chemistry/metabolism ; Protein Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-06-16
    Description: The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watkins, R E -- Wisely, G B -- Moore, L B -- Collins, J L -- Lambert, M H -- Williams, S P -- Willson, T M -- Kliewer, S A -- Redinbo, M R -- New York, N.Y. -- Science. 2001 Jun 22;292(5525):2329-33. Epub 2001 Jun 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina (UNC) at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11408620" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Diphosphonates/chemistry/*metabolism ; Humans ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cytoplasmic and Nuclear/*chemistry/*metabolism ; Receptors, Steroid/*chemistry/*metabolism ; Rifampin/metabolism ; Xenobiotics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-11-26
    Description: Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818760/" 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/PMC2818760/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Lenny -- White, David W -- Gross, Stefan -- Bennett, Bryson D -- Bittinger, Mark A -- Driggers, Edward M -- Fantin, Valeria R -- Jang, Hyun Gyung -- Jin, Shengfang -- Keenan, Marie C -- Marks, Kevin M -- Prins, Robert M -- Ward, Patrick S -- Yen, Katharine E -- Liau, Linda M -- Rabinowitz, Joshua D -- Cantley, Lewis C -- Thompson, Craig B -- Vander Heiden, Matthew G -- Su, Shinsan M -- P01 CA104838/CA/NCI NIH HHS/ -- P01 CA104838-05/CA/NCI NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- R01 CA105463-06/CA/NCI NIH HHS/ -- R21 CA128620/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):739-44. doi: 10.1038/nature08617. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19935646" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/genetics ; Brain Neoplasms/*genetics/*metabolism/pathology ; Catalytic Domain ; Cell Line ; Crystallography, X-Ray ; Disease Progression ; Enzyme Assays ; Glioma/genetics/metabolism/pathology ; Glutarates/*metabolism ; Histidine/genetics/metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Models, Molecular ; Mutant Proteins/*genetics/*metabolism ; Mutation/genetics ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Exploitation of binding energy for catalysis and design (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-30
    Description: Enzymes use substrate-binding energy both to promote ground-state association and to stabilize the reaction transition state selectively. The monomeric homing endonuclease I-AniI cleaves with high sequence specificity in the centre of a 20-base-pair (bp) DNA target site, with the amino (N)-terminal domain of the enzyme making extensive binding interactions with the left (-) side of the target site and the similarly structured carboxy (C)-terminal domain interacting with the right (+) side. Here we show that, despite the approximate twofold symmetry of the enzyme-DNA complex, there is almost complete segregation of interactions responsible for substrate binding to the (-) side of the interface and interactions responsible for transition-state stabilization to the (+) side. Although single base-pair substitutions throughout the entire DNA target site reduce catalytic efficiency, mutations in the (-) DNA half-site almost exclusively increase the dissociation constant (K(D)) and the Michaelis constant under single-turnover conditions (K(M)*), and those in the (+) half-site primarily decrease the turnover number (k(cat)*). The reduction of activity produced by mutations on the (-) side, but not mutations on the (+) side, can be suppressed by tethering the substrate to the endonuclease displayed on the surface of yeast. This dramatic asymmetry in the use of enzyme-substrate binding energy for catalysis has direct relevance to the redesign of endonucleases to cleave genomic target sites for gene therapy and other applications. Computationally redesigned enzymes that achieve new specificities on the (-) side do so by modulating K(M)*, whereas redesigns with altered specificities on the (+) side modulate k(cat)*. Our results illustrate how classical enzymology and modern protein design can each inform the other.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771326/" 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/PMC2771326/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thyme, Summer B -- Jarjour, Jordan -- Takeuchi, Ryo -- Havranek, James J -- Ashworth, Justin -- Scharenberg, Andrew M -- Stoddard, Barry L -- Baker, David -- GM084433/GM/NIGMS NIH HHS/ -- R00 RR024107/RR/NCRR NIH HHS/ -- R00 RR024107-03/RR/NCRR NIH HHS/ -- R00 RR024107-04/RR/NCRR NIH HHS/ -- RL1 GM084433/GM/NIGMS NIH HHS/ -- RL1 GM084433-03/GM/NIGMS NIH HHS/ -- RL1CA133832/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Oct 29;461(7268):1300-4. doi: 10.1038/nature08508.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. sthyme@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865174" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; *Biocatalysis ; Computational Biology ; *Computer Simulation ; DNA/chemistry/metabolism ; Endonucleases/chemistry/*metabolism ; Kinetics ; Models, Molecular ; Protein Binding ; Protein Conformation ; RNA-Directed DNA Polymerase/chemistry/*metabolism ; Saccharomyces cerevisiae/metabolism ; Substrate Specificity ; *Thermodynamics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-02-20
    Description: The complement system is an essential component of the innate and acquired immune system, and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref. 2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface. Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670278/" 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/PMC2670278/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schneider, Muriel C -- Prosser, Beverly E -- Caesar, Joseph J E -- Kugelberg, Elisabeth -- Li, Su -- Zhang, Qian -- Quoraishi, Sadik -- Lovett, Janet E -- Deane, Janet E -- Sim, Robert B -- Roversi, Pietro -- Johnson, Steven -- Tang, Christoph M -- Lea, Susan M -- 083599/Wellcome Trust/United Kingdom -- G0400775/Medical Research Council/United Kingdom -- G0400775(71657)/Medical Research Council/United Kingdom -- G0500367/Medical Research Council/United Kingdom -- G0601195/Medical Research Council/United Kingdom -- G0601195(79743)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 16;458(7240):890-3. doi: 10.1038/nature07769. Epub 2009 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Molecular Microbiology and Infection, Imperial College, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225461" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Bacterial/*chemistry/*metabolism ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Carbohydrates/*chemistry ; Complement Factor H/*chemistry/immunology/*metabolism ; Crystallography, X-Ray ; Ligands ; Models, Molecular ; *Molecular Mimicry ; Neisseria meningitidis/chemistry/immunology/*metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Structure-Activity Relationship ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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