2hvh: Difference between revisions
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<StructureSection load='2hvh' size='340' side='right'caption='[[2hvh]], [[Resolution|resolution]] 2.49Å' scene=''> | <StructureSection load='2hvh' size='340' side='right'caption='[[2hvh]], [[Resolution|resolution]] 2.49Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2hvh]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2hvh]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HVH FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.492Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6OG:6-O-METHYL+GUANOSINE-5-MONOPHOSPHATE'>6OG</scene>, <scene name='pdbligand=DCT:2,3-DIDEOXYCYTIDINE+5-TRIPHOSPHATE'>DCT</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
< | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvh OCA], [https://pdbe.org/2hvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hvh RCSB], [https://www.ebi.ac.uk/pdbsum/2hvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hvh ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvh OCA], [https://pdbe.org/2hvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hvh RCSB], [https://www.ebi.ac.uk/pdbsum/2hvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hvh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q45458_GEOSE Q45458_GEOSE] In addition to polymerase activity, this DNA polymerase exhibits 5'-3' exonuclease activity.[RuleBase:RU004460] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</div> | </div> | ||
<div class="pdbe-citations 2hvh" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2hvh" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Geobacillus stearothermophilus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Beese | [[Category: Beese LS]] | ||
[[Category: Forsberg | [[Category: Forsberg LJ]] | ||
[[Category: Warren | [[Category: Warren JJ]] | ||
Latest revision as of 13:02, 30 August 2023
ddCTP:O6MeG pair in the polymerase active site (0 position)ddCTP:O6MeG pair in the polymerase active site (0 position)
Structural highlights
FunctionQ45458_GEOSE In addition to polymerase activity, this DNA polymerase exhibits 5'-3' exonuclease activity.[RuleBase:RU004460] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMethylating agents are widespread environmental carcinogens that generate a broad spectrum of DNA damage. Methylation at the guanine O(6) position confers the greatest mutagenic and carcinogenic potential. DNA polymerases insert cytosine and thymine with similar efficiency opposite O(6)-methyl-guanine (O6MeG). We combined pre-steady-state kinetic analysis and a series of nine x-ray crystal structures to contrast the reaction pathways of accurate and mutagenic replication of O6MeG in a high-fidelity DNA polymerase from Bacillus stearothermophilus. Polymerases achieve substrate specificity by selecting for nucleotides with shape and hydrogen-bonding patterns that complement a canonical DNA template. Our structures reveal that both thymine and cytosine O6MeG base pairs evade proofreading by mimicking the essential molecular features of canonical substrates. The steric mimicry depends on stabilization of a rare cytosine tautomer in C.O6MeG-polymerase complexes. An unusual electrostatic interaction between O-methyl protons and a thymine carbonyl oxygen helps stabilize T.O6MeG pairs bound to DNA polymerase. Because DNA methylators constitute an important class of chemotherapeutic agents, the molecular mechanisms of replication of these DNA lesions are important for our understanding of both the genesis and treatment of cancer. The structural basis for the mutagenicity of O(6)-methyl-guanine lesions.,Warren JJ, Forsberg LJ, Beese LS Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19701-6. Epub 2006 Dec 18. PMID:17179038[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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