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| | ==Solution Structure of the Lyase Domain of Human DNA Polymerase Lambda== | | ==Solution Structure of the Lyase Domain of Human DNA Polymerase Lambda== |
| - | <StructureSection load='1nzp' size='340' side='right' caption='[[1nzp]], [[NMR_Ensembles_of_Models | 8 NMR models]]' scene=''> | + | <StructureSection load='1nzp' size='340' side='right'caption='[[1nzp]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1nzp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NZP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1nzp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZP FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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'>[https://proteopedia.org/fgij/fg.htm?mol=1nzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzp OCA], [https://pdbe.org/1nzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nzp RCSB], [https://www.ebi.ac.uk/pdbsum/1nzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nzp 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=1nzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nzp OCA], [http://pdbe.org/1nzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nzp RCSB], [http://www.ebi.ac.uk/pdbsum/1nzp PDBsum]</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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nz/1nzp_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nz/1nzp_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nzp ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[DNA polymerase|DNA polymerase]] | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed DNA polymerase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Bebenek, K]] | + | [[Category: Bebenek K]] |
| - | [[Category: Blanco, L]] | + | [[Category: Blanco L]] |
| - | [[Category: DeRose, E F]] | + | [[Category: DeRose EF]] |
| - | [[Category: Garcia-Diaz, M]] | + | [[Category: Garcia-Diaz M]] |
| - | [[Category: Kirby, T W]] | + | [[Category: Kirby TW]] |
| - | [[Category: Kunkel, T A]] | + | [[Category: Kunkel TA]] |
| - | [[Category: London, R E]] | + | [[Category: London RE]] |
| - | [[Category: Mueller, G A]] | + | [[Category: Mueller GA]] |
| - | [[Category: Kda domain]]
| + | |
| - | [[Category: Dna binding protein-transferase complex]]
| + | |
| - | [[Category: Dna polymerase lambda]]
| + | |
| - | [[Category: Lyase domain]]
| + | |
| - | [[Category: Pol beta-like]]
| + | |
| - | [[Category: Pol lambda]]
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| 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]
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 PubMed
DNA polymerase lambda (pol lambda) is a recently discovered nuclear enzyme belonging to the pol X family of DNA polymerases that exhibits a 32% sequence identity with the nuclear DNA repair protein, pol beta. Structural modeling suggests that pol lambda contains the palm, fingers, thumb, and 8 kDa lyase domains present in pol beta, as well as an additional N-terminal BRCT domain and a serine-proline-rich linker that are presumably involved in protein-protein interactions. The 8 kDa domain of pol beta is important for DNA binding and contains the dRP lyase activity, which is the rate-limiting step in the single-nucleotide base excision repair (BER) pathway of damaged DNA. Recently, it was shown that the 8 kDa domain of pol lambda also contains the dRP lyase activity. To gain further insight into the catalytic mechanism of dRP removal by pol lambda, we have determined the solution structure of the 8 kDa lyase domain of human DNA pol lambda via multidimensional NMR methods and the ARIA program. The resulting structures exhibited a high degree of similarity with the 8 kDa lyase domain of pol beta. Specifically, the side chains of residues W274, R275, Y279, K307, R308, and K312 are in similar positions to the functionally important side chains of residues H34, K35, Y39, K60, K68, and K72 in the 8 kDa lyase domain of pol beta. This suggests that, on the basis of the proposed roles of these residues in pol beta, the corresponding pol lambda side chains may be involved in DNA binding and dRP lyase activity. The structural alignment of W274 (pol lambda) with H34 (pol beta) indicates that the former is probably involved in a similar base stacking interaction with template DNA at the position of the gap, in contrast with several previous proposals which aligned D272 with H34. In a few cases for which there is a nonconservative substitution in the sequence alignment, a structural comparison shows a positionally and, hence, probably a functionally equivalent residue, e.g., K60 in pol beta and K307 in pol lambda. Additionally, on the basis of the structural alignment obtained, several previously proposed mechanistic hypotheses can be evaluated.
Solution structure of the lyase domain of human DNA polymerase lambda.,DeRose EF, Kirby TW, Mueller GA, Bebenek K, Garcia-Diaz M, Blanco L, Kunkel TA, London RE Biochemistry. 2003 Aug 19;42(32):9564-74. PMID:12911298[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
- ↑ DeRose EF, Kirby TW, Mueller GA, Bebenek K, Garcia-Diaz M, Blanco L, Kunkel TA, London RE. Solution structure of the lyase domain of human DNA polymerase lambda. Biochemistry. 2003 Aug 19;42(32):9564-74. PMID:12911298 doi:http://dx.doi.org/10.1021/bi034298s
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