4eyh: Difference between revisions
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==Human DNA polymerase iota incorporating dCTP opposite N-(deoxyguanosin-8-yl)-1-aminopyrene lesion== | ==Human DNA polymerase iota incorporating dCTP opposite N-(deoxyguanosin-8-yl)-1-aminopyrene lesion== | ||
<StructureSection load='4eyh' size='340' side='right' caption='[[4eyh]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='4eyh' size='340' side='right'caption='[[4eyh]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4eyh]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4eyh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EYH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=DG8:2-DEOXY-8-(PYREN-1-YLAMINO)GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>DG8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4eyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eyh OCA], [https://pdbe.org/4eyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eyh RCSB], [https://www.ebi.ac.uk/pdbsum/4eyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eyh ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/POLI_HUMAN POLI_HUMAN] Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.<ref>PMID:11013228</ref> <ref>PMID:11251121</ref> <ref>PMID:11387224</ref> <ref>PMID:12410315</ref> <ref>PMID:14630940</ref> <ref>PMID:15199127</ref> <ref>PMID:15254543</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4eyh" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4eyh" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Kirouac | [[Category: Kirouac K]] | ||
[[Category: Ling | [[Category: Ling H]] | ||
Revision as of 07:22, 7 October 2022
Human DNA polymerase iota incorporating dCTP opposite N-(deoxyguanosin-8-yl)-1-aminopyrene lesionHuman DNA polymerase iota incorporating dCTP opposite N-(deoxyguanosin-8-yl)-1-aminopyrene lesion
Structural highlights
FunctionPOLI_HUMAN Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedNitrated polycyclic aromatic hydrocarbons are common environmental pollutants, of which many are mutagenic and carcinogenic. 1-Nitropyrene is the most abundant nitrated polycyclic aromatic hydrocarbon, which causes DNA damage and is carcinogenic in experimental animals. Error-prone translesion synthesis of 1-nitropyrene-derived DNA lesions generates mutations that likely play a role in the etiology of cancer. Here, we report two crystal structures of the human Y-family DNA polymerase iota complexed with the major 1-nitropyrene DNA lesion at the insertion stage, incorporating either dCTP or dATP nucleotide opposite the lesion. Poliota maintains the adduct in its active site in two distinct conformations. dCTP forms a Watson-Crick base pair with the adducted guanine and excludes the pyrene ring from the helical DNA, which inhibits replication beyond the lesion. By contrast, the mismatched dATP stacks above the pyrene ring that is intercalated in the helix and achieves a productive conformation for misincorporation. The intra-helical bulky pyrene mimics a base pair in the active site and facilitates adenine misincorporation. By structure-based mutagenesis, we show that the restrictive active site of human poleta prevents the intra-helical conformation and A-base misinsertions. This work provides one of the molecular mechanisms for G to T transversions, a signature mutation in human lung cancer. Replication of a carcinogenic nitropyrene DNA lesion by human Y-family DNA polymerase.,Kirouac KN, Basu AK, Ling H Nucleic Acids Res. 2012 Dec 24. PMID:23268450[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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