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| | <StructureSection load='4xus' size='340' side='right'caption='[[4xus]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4xus' size='340' side='right'caption='[[4xus]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xus]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XUS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xus]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XUS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4xus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xus OCA], [https://pdbe.org/4xus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xus RCSB], [https://www.ebi.ac.uk/pdbsum/4xus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xus ProSAT]</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=4xus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xus OCA], [http://pdbe.org/4xus PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xus RCSB], [http://www.ebi.ac.uk/pdbsum/4xus PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xus ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DPOLL_HUMAN DPOLL_HUMAN]] Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.<ref>PMID:11457865</ref> <ref>PMID:15537631</ref> | + | [https://www.uniprot.org/uniprot/DPOLL_HUMAN DPOLL_HUMAN] Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.<ref>PMID:11457865</ref> <ref>PMID:15537631</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 4xus" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4xus" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Burak, M J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Garcia-Diaz, M]] | + | [[Category: Burak MJ]] |
| - | [[Category: Guja, K E]] | + | [[Category: Garcia-Diaz M]] |
| - | [[Category: Dna polymerase lambda]]
| + | [[Category: Guja KE]] |
| - | [[Category: Helix-hairpin-helix]]
| + | |
| - | [[Category: Protein-dna complex]] | + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| Structural highlights
Function
DPOLL_HUMAN Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.[1] [2]
Publication Abstract from PubMed
8-Oxo-7,8,-dihydro-2'-deoxyguanosine triphosphate (8-oxo-dGTP) is a major product of oxidative damage in the nucleotide pool. It is capable of mispairing with adenosine (dA), resulting in futile, mutagenic cycles of base excision repair. Therefore, it is critical that DNA polymerases discriminate against 8-oxo-dGTP at the insertion step. Because of its roles in oxidative DNA damage repair and non-homologous end joining, DNA polymerase lambda (Pol lambda) may frequently encounter 8-oxo-dGTP. Here, we have studied the mechanisms of 8-oxo-dGMP incorporation and discrimination by Pol lambda. We have solved high resolution crystal structures showing how Pol lambda accommodates 8-oxo-dGTP in its active site. The structures indicate that when mispaired with dA, the oxidized nucleotide assumes the mutagenic syn-conformation, and is stabilized by multiple interactions. Steady-state kinetics reveal that two residues lining the dNTP binding pocket, Ala(510) and Asn(513), play differential roles in dNTP selectivity. Specifically, Ala(510) and Asn(513) facilitate incorporation of 8-oxo-dGMP opposite dA and dC, respectively. These residues also modulate the balance between purine and pyrimidine incorporation. Our results shed light on the mechanisms controlling 8-oxo-dGMP incorporation in Pol lambda and on the importance of interactions with the incoming dNTP to determine selectivity in family X DNA polymerases.
Nucleotide binding interactions modulate dNTP selectivity and facilitate 8-oxo-dGTP incorporation by DNA polymerase lambda.,Burak MJ, Guja KE, Garcia-Diaz M Nucleic Acids Res. 2015 Sep 18;43(16):8089-99. doi: 10.1093/nar/gkv760. Epub 2015, Jul 28. PMID:26220180[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garcia-Diaz M, Bebenek K, Kunkel TA, Blanco L. Identification of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in human DNA polymerase lambda: a possible role in base excision repair. J Biol Chem. 2001 Sep 14;276(37):34659-63. Epub 2001 Jul 16. PMID:11457865 doi:10.1074/jbc.M106336200
- ↑ Maga G, Ramadan K, Locatelli GA, Shevelev I, Spadari S, Hubscher U. DNA elongation by the human DNA polymerase lambda polymerase and terminal transferase activities are differentially coordinated by proliferating cell nuclear antigen and replication protein A. J Biol Chem. 2005 Jan 21;280(3):1971-81. Epub 2004 Nov 10. PMID:15537631 doi:10.1074/jbc.M411650200
- ↑ Burak MJ, Guja KE, Garcia-Diaz M. Nucleotide binding interactions modulate dNTP selectivity and facilitate 8-oxo-dGTP incorporation by DNA polymerase lambda. Nucleic Acids Res. 2015 Sep 18;43(16):8089-99. doi: 10.1093/nar/gkv760. Epub 2015, Jul 28. PMID:26220180 doi:http://dx.doi.org/10.1093/nar/gkv760
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