3osn
From Proteopedia
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| - | [[ | + | ==Structural Basis for Proficient Incorporation of dTTP Opposite O6-Methylguanine by Human DNA Polymerase Iota== |
| + | <StructureSection load='3osn' size='340' side='right' caption='[[3osn]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3osn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OSN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OSN FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2alz|2alz]], [[3epg|3epg]], [[3epi|3epi]], [[2fll|2fll]], [[3ngd|3ngd]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLI, RAD30B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3osn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3osn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3osn RCSB], [http://www.ebi.ac.uk/pdbsum/3osn PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | O(6)-methylguanine (O(6)-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase iota core enzyme was determined for nucleoside triphosphate incorporation opposite O(6)-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol iota, which showed that dTTP incorporation occurs with high efficiency opposite O(6)-methylG. Misincorporation of dTTP opposite O(6)-methylG occurred with approximately 6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol iota with O(6)-methylG as the template base and incoming dCTP or dTTP were solved and showed that O(6)-methylG is rotated into the syn conformation in the pol iota active site and that dTTP misincorporation by pol iota is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O(6)-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O(6)-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O(6) atoms of O(6)-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O(6)-methylG by human pol iota, in contrast to the mispairing modes observed previously for O(6)-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I. | ||
| - | + | Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota.,Pence MG, Choi JY, Egli M, Guengerich FP J Biol Chem. 2010 Dec 24;285(52):40666-72. Epub 2010 Oct 20. PMID:20961860<ref>PMID:20961860</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[DNA polymerase|DNA polymerase]] | *[[DNA polymerase|DNA polymerase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Pence, M G | + | [[Category: Pence, M G]] |
[[Category: Hoogsteen base pair]] | [[Category: Hoogsteen base pair]] | ||
[[Category: Nucleoside triphosphate]] | [[Category: Nucleoside triphosphate]] | ||
Revision as of 10:37, 9 December 2014
Structural Basis for Proficient Incorporation of dTTP Opposite O6-Methylguanine by Human DNA Polymerase Iota
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