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 [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2hvh]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_12980 Atcc 12980]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HVH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCT:2,3-DIDEOXYCYTIDINE+5-TRIPHOSPHATE'>DCT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCT:2,3-DIDEOXYCYTIDINE+5-TRIPHOSPHATE'>DCT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6OG:6-O-METHYL+GUANOSINE-5-MONOPHOSPHATE'>6OG</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6OG:6-O-METHYL+GUANOSINE-5-MONOPHOSPHATE'>6OG</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hhw|2hhw]], [[2hhv|2hhv]], [[2hhu|2hhu]], [[2hht|2hht]], [[2hhs|2hhs]], [[2hhx|2hhx]], [[2hhy|2hhy]], [[2hhq|2hhq]], [[2hvi|2hvi]], [[2hw3|2hw3]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hhw|2hhw]], [[2hhv|2hhv]], [[2hhu|2hhu]], [[2hht|2hht]], [[2hhs|2hhs]], [[2hhx|2hhx]], [[2hhy|2hhy]], [[2hhq|2hhq]], [[2hvi|2hvi]], [[2hw3|2hw3]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">polA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1422 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">polA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1422 ATCC 12980])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hvh RCSB], [http://www.ebi.ac.uk/pdbsum/2hvh PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hvh OCA], [http://pdbe.org/2hvh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hvh RCSB], [http://www.ebi.ac.uk/pdbsum/2hvh PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2hvh" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Atcc 12980]] | |||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Beese, L S]] | [[Category: Beese, L S]] | ||
[[Category: Forsberg, L J]] | [[Category: Forsberg, L J]] | ||
Revision as of 17:27, 11 September 2015
ddCTP:O6MeG pair in the polymerase active site (0 position)ddCTP:O6MeG pair in the polymerase active site (0 position)
Structural highlights
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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