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  • History, Ancient  (15)
  • Protein Conformation  (14)
  • Nature Publishing Group (NPG)  (29)
  • American Association for the Advancement of Science
  • 2005-2009  (29)
  • 1940-1944
  • 2009  (29)
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  • 2005-2009  (29)
  • 1940-1944
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  • 2009  (29)
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  • 2008  (15)
  • 1
    Publication Date: 2009-03-20
    Description: Thirty years after oxygen isotope records from microfossils deposited in ocean sediments confirmed the hypothesis that variations in the Earth's orbital geometry control the ice ages, fundamental questions remain over the response of the Antarctic ice sheets to orbital cycles. Furthermore, an understanding of the behaviour of the marine-based West Antarctic ice sheet (WAIS) during the 'warmer-than-present' early-Pliocene epoch ( approximately 5-3 Myr ago) is needed to better constrain the possible range of ice-sheet behaviour in the context of future global warming. Here we present a marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf by the ANDRILL programme and demonstrate well-dated, approximately 40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth's axial tilt (obliquity) during the Pliocene. Our data provide direct evidence for orbitally induced oscillations in the WAIS, which periodically collapsed, resulting in a switch from grounded ice, or ice shelves, to open waters in the Ross embayment when planetary temperatures were up to approximately 3 degrees C warmer than today and atmospheric CO(2) concentration was as high as approximately 400 p.p.m.v. (refs 5, 6). The evidence is consistent with a new ice-sheet/ice-shelf model that simulates fluctuations in Antarctic ice volume of up to +7 m in equivalent sea level associated with the loss of the WAIS and up to +3 m in equivalent sea level from the East Antarctic ice sheet, in response to ocean-induced melting paced by obliquity. During interglacial times, diatomaceous sediments indicate high surface-water productivity, minimal summer sea ice and air temperatures above freezing, suggesting an additional influence of surface melt under conditions of elevated CO(2).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naish, T -- Powell, R -- Levy, R -- Wilson, G -- Scherer, R -- Talarico, F -- Krissek, L -- Niessen, F -- Pompilio, M -- Wilson, T -- Carter, L -- DeConto, R -- Huybers, P -- McKay, R -- Pollard, D -- Ross, J -- Winter, D -- Barrett, P -- Browne, G -- Cody, R -- Cowan, E -- Crampton, J -- Dunbar, G -- Dunbar, N -- Florindo, F -- Gebhardt, C -- Graham, I -- Hannah, M -- Hansaraj, D -- Harwood, D -- Helling, D -- Henrys, S -- Hinnov, L -- Kuhn, G -- Kyle, P -- Laufer, A -- Maffioli, P -- Magens, D -- Mandernack, K -- McIntosh, W -- Millan, C -- Morin, R -- Ohneiser, C -- Paulsen, T -- Persico, D -- Raine, I -- Reed, J -- Riesselman, C -- Sagnotti, L -- Schmitt, D -- Sjunneskog, C -- Strong, P -- Taviani, M -- Vogel, S -- Wilch, T -- Williams, T -- England -- Nature. 2009 Mar 19;458(7236):322-8. doi: 10.1038/nature07867.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Antarctic Research Centre, Victoria University of Wellington, Kelburn Parade, PO Box 600, Wellington 6012, New Zealand. tim.naish@vuw.ac.nz〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295607" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Atmosphere/analysis/chemistry ; Calibration ; Carbon Dioxide/analysis ; Diatoms/chemistry/isolation & purification ; Fossils ; History, Ancient ; *Ice Cover ; Oxygen Isotopes ; Temperature
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  • 2
    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
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  • 3
    Publication Date: 2009-06-12
    Description: Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O(6)-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O(6)-methylguanine or cigarette-smoke-derived O(6)-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life. Genetic connections to mammalian XPG (also known as ERCC5) and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions with Escherichia coli UvrA and UvrC combined with structural results reveal that ATLs sculpt alkylated DNA to create a genetic and structural intersection of base damage processing with nucleotide excision repair.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729916/" 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/PMC2729916/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tubbs, Julie L -- Latypov, Vitaly -- Kanugula, Sreenivas -- Butt, Amna -- Melikishvili, Manana -- Kraehenbuehl, Rolf -- Fleck, Oliver -- Marriott, Andrew -- Watson, Amanda J -- Verbeek, Barbara -- McGown, Gail -- Thorncroft, Mary -- Santibanez-Koref, Mauro F -- Millington, Christopher -- Arvai, Andrew S -- Kroeger, Matthew D -- Peterson, Lisa A -- Williams, David M -- Fried, Michael G -- Margison, Geoffrey P -- Pegg, Anthony E -- Tainer, John A -- CA018137/CA/NCI NIH HHS/ -- CA097209/CA/NCI NIH HHS/ -- CA59887/CA/NCI NIH HHS/ -- GM070662/GM/NIGMS NIH HHS/ -- R01 CA059887/CA/NCI NIH HHS/ -- R01 CA059887-12/CA/NCI NIH HHS/ -- R01 CA059887-13/CA/NCI NIH HHS/ -- R01 GM070662/GM/NIGMS NIH HHS/ -- R01 GM070662-01/GM/NIGMS NIH HHS/ -- R01 GM070662-02/GM/NIGMS NIH HHS/ -- R01 GM070662-03/GM/NIGMS NIH HHS/ -- R01 GM070662-04/GM/NIGMS NIH HHS/ -- R01 GM070662-05/GM/NIGMS NIH HHS/ -- R01 GM070662-06/GM/NIGMS NIH HHS/ -- Cancer Research UK/United Kingdom -- England -- Nature. 2009 Jun 11;459(7248):808-13. doi: 10.1038/nature08076.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19516334" target="_blank"〉PubMed〈/a〉
    Keywords: Alkyl and Aryl Transferases/*chemistry/*metabolism ; Alkylation ; Binding Sites ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; *DNA Damage ; *DNA Repair ; Guanine/analogs & derivatives/chemistry/metabolism ; Humans ; Models, Molecular ; Protein Binding ; Protein Conformation
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  • 4
    Publication Date: 2009-05-12
    Description: Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697266/" 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/PMC2697266/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Gang G -- Song, Jikui -- Wang, Zhanxin -- Dormann, Holger L -- Casadio, Fabio -- Li, Haitao -- Luo, Jun-Li -- Patel, Dinshaw J -- Allis, C David -- K99 CA151683/CA/NCI NIH HHS/ -- R37 GM053512/GM/NIGMS NIH HHS/ -- R37 GM053512-30/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jun 11;459(7248):847-51. doi: 10.1038/nature08036.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19430464" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics/physiology ; Animals ; Cell Transformation, Neoplastic ; Cells, Cultured ; Chromatin/*metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Genes, Homeobox/genetics ; Hematologic Neoplasms/genetics/*metabolism/*pathology ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/metabolism/pathology ; Histones/chemistry/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/*chemistry/genetics/*metabolism ; Lysine/metabolism ; Magnetic Resonance Spectroscopy ; Methylation ; Mice ; Models, Molecular ; Nuclear Pore Complex Proteins/chemistry/genetics/metabolism ; Oncogene Proteins, Fusion/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Conformation ; Retinoblastoma-Binding Protein 2 ; Transcription, Genetic ; Tumor Suppressor Proteins/*chemistry/genetics/*metabolism
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  • 5
    Publication Date: 2009-02-11
    Description: Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 A resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 A (ref. 2). A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and beta-sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol(-1) of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765791/" 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/PMC2765791/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gertsman, Ilya -- Gan, Lu -- Guttman, Miklos -- Lee, Kelly -- Speir, Jeffrey A -- Duda, Robert L -- Hendrix, Roger W -- Komives, Elizabeth A -- Johnson, John E -- GM08326/GM/NIGMS NIH HHS/ -- R01 AI040101/AI/NIAID NIH HHS/ -- R01 AI040101-04/AI/NIAID NIH HHS/ -- R01 AI040101-14/AI/NIAID NIH HHS/ -- R01 AI40101/AI/NIAID NIH HHS/ -- R01 GM47795/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 2;458(7238):646-50. doi: 10.1038/nature07686. Epub 2009 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19204733" target="_blank"〉PubMed〈/a〉
    Keywords: Capsid/*chemistry/*metabolism ; Capsid Proteins/chemistry/genetics/metabolism ; Crystallography, X-Ray ; Deuterium Exchange Measurement ; Models, Molecular ; Movement ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Siphoviridae/*chemistry/genetics/*growth & development ; Thermodynamics ; *Virus Assembly
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  • 6
    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rockstrom, Johan -- Steffen, Will -- Noone, Kevin -- Persson, Asa -- Chapin, F Stuart 3rd -- Lambin, Eric F -- Lenton, Timothy M -- Scheffer, Marten -- Folke, Carl -- Schellnhuber, Hans Joachim -- Nykvist, Bjorn -- de Wit, Cynthia A -- Hughes, Terry -- van der Leeuw, Sander -- Rodhe, Henning -- Sorlin, Sverker -- Snyder, Peter K -- Costanza, Robert -- Svedin, Uno -- Falkenmark, Malin -- Karlberg, Louise -- Corell, Robert W -- Fabry, Victoria J -- Hansen, James -- Walker, Brian -- Liverman, Diana -- Richardson, Katherine -- Crutzen, Paul -- Foley, Jonathan A -- England -- Nature. 2009 Sep 24;461(7263):472-5. doi: 10.1038/461472a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stockholm Resilience Centre, Stockholm University, Kraftriket 2B, 10691 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779433" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Civilization ; Conservation of Natural Resources/*methods/trends ; *Earth (Planet) ; Ecology/*methods/*trends ; *Ecosystem ; Extinction, Biological ; Fossils ; Green Chemistry Technology/*methods/trends ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Human Activities/history ; Humans ; Nitrogen/metabolism ; Phosphorus/metabolism
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  • 7
    Publication Date: 2009-05-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothschild, Lynn J -- England -- Nature. 2009 May 21;459(7245):335-6. doi: 10.1038/459335a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458704" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Evolution ; *Earth (Planet) ; History, Ancient ; Hot Temperature ; *Meteoroids ; *Models, Biological ; Moon ; *Origin of Life ; Silicates/analysis ; Sterilization ; Time Factors ; Zirconium/analysis
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  • 8
    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
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  • 9
    Publication Date: 2009-07-10
    Description: Many aspects of the carbon cycle can be assessed from temporal changes in the (13)C/(12)C ratio of oceanic bicarbonate. (13)C/(12)C can temporarily rise when large amounts of (13)C-depleted photosynthetic organic matter are buried at enhanced rates, and can decrease if phytomass is rapidly oxidized or if low (13)C is rapidly released from methane clathrates. Assuming that variations of the marine (13)C/(12)C ratio are directly recorded in carbonate rocks, thousands of carbon isotope analyses of late Precambrian examples have been published to correlate these otherwise undatable strata and to document perturbations to the carbon cycle just before the great expansion of metazoan life. Low (13)C/(12)C in some Neoproterozoic carbonates is considered evidence of carbon cycle perturbations unique to the Precambrian. These include complete oxidation of all organic matter in the ocean and complete productivity collapse such that low-(13)C/(12)C hydrothermal CO(2) becomes the main input of carbon. Here we compile all published oxygen and carbon isotope data for Neoproterozoic marine carbonates, and consider them in terms of processes known to alter the isotopic composition during transformation of the initial precipitate into limestone/dolostone. We show that the combined oxygen and carbon isotope systematics are identical to those of well-understood Phanerozoic examples that lithified in coastal pore fluids, receiving a large groundwater influx of photosynthetic carbon from terrestrial phytomass. Rather than being perturbations to the carbon cycle, widely reported decreases in (13)C/(12)C in Neoproterozoic carbonates are more easily interpreted in the same way as is done for Phanerozoic examples. This influx of terrestrial carbon is not apparent in carbonates older than approximately 850 Myr, so we infer an explosion of photosynthesizing communities on late Precambrian land surfaces. As a result, biotically enhanced weathering generated carbon-bearing soils on a large scale and their detrital sedimentation sequestered carbon. This facilitated a rise in O(2) necessary for the expansion of multicellular life.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knauth, L Paul -- Kennedy, Martin J -- England -- Nature. 2009 Aug 6;460(7256):728-32. doi: 10.1038/nature08213. Epub 2009 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Earth and Space Exploration, Arizona State University, Tempe, Arizona 85287-1404, USA. Knauth@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587681" target="_blank"〉PubMed〈/a〉
    Keywords: Biomass ; Calcium Carbonate/chemistry ; Carbon/chemistry/*metabolism ; Carbon Isotopes ; Carbonates/*analysis/*chemistry ; Earth (Planet) ; Geologic Sediments/*chemistry ; History, Ancient ; Magnesium/chemistry ; Oceans and Seas ; Oxygen/analysis/metabolism ; Oxygen Isotopes ; *Photosynthesis ; Plants/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2009-12-17
    Description: Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799227/" 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/PMC2799227/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Min -- Chong, Yeeting E -- Shapiro, Ryan -- Beebe, Kirk -- Yang, Xiang-Lei -- Schimmel, Paul -- GM 15539/GM/NIGMS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- R01 GM015539-43/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):808-12. doi: 10.1038/nature08612.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010690" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/*metabolism ; Alanine-tRNA Ligase/chemistry/genetics/*metabolism ; Aspartic Acid/genetics/metabolism ; Catalytic Domain ; Crystallization ; Escherichia coli/*enzymology ; Kinetics ; Models, Molecular ; Mutation ; *Protein Biosynthesis ; Protein Conformation ; RNA, Transfer, Ala/metabolism ; Serine/*metabolism ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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