4pha

From Proteopedia

(Difference between revisions)

Revision as of 00:25, 25 December 2014

Structure of human DNA polymerase beta complexed with A in the template base paired with incoming non-hydrolyzable CTP

Structural highlights

4pha is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[DPOLB_HUMAN] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta (polbeta), we report four crystal structures of polbeta complexed with dG*dTTP and dA*dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA*dCTP-Mg2+ complex adopts an 'intermediate' protein conformation while the dG*dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound 'pre-chemistry-state' structures show that the dA*dCTP-Mn2+ complex is structurally very similar to the dA*dCTP-Mg2+ complex, whereas the dG*dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson-Crick-like dG*dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polbeta increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polbeta appears to allow only a Watson-Crick-like conformation for purine*pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson-Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polbeta.

The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta,Koag MC, Nam K, Lee S Nucleic Acids Res. 2014 Sep 8. pii: gku789. PMID:25200079^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bennett RA, Wilson DM 3rd, Wong D, Demple B. Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. PMID:9207062
↑ Matsumoto Y, Kim K, Katz DS, Feng JA. Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate groups. Biochemistry. 1998 May 5;37(18):6456-64. PMID:9572863 doi:10.1021/bi9727545
↑ DeMott MS, Beyret E, Wong D, Bales BC, Hwang JT, Greenberg MM, Demple B. Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone. J Biol Chem. 2002 Mar 8;277(10):7637-40. Epub 2002 Jan 22. PMID:11805079 doi:10.1074/jbc.C100577200
↑ Parsons JL, Dianova II, Khoronenkova SV, Edelmann MJ, Kessler BM, Dianov GL. USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase beta. Mol Cell. 2011 Mar 4;41(5):609-15. doi: 10.1016/j.molcel.2011.02.016. PMID:21362556 doi:10.1016/j.molcel.2011.02.016
↑ Koag MC, Nam K, Lee S. The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta Nucleic Acids Res. 2014 Sep 8. pii: gku789. PMID:25200079 doi:http://dx.doi.org/10.1093/nar/gku789

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4pha"

Categories: Koag, M C | Lee, S | Human dna polymerase beta

@@ Line 6: / Line 6: @@
 <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=4pha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pha OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pha RCSB], [http://www.ebi.ac.uk/pdbsum/4pha PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/DPOLB_HUMAN DPOLB_HUMAN]] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.<ref>PMID:9207062</ref> <ref>PMID:9572863</ref> <ref>PMID:11805079</ref> <ref>PMID:21362556</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 20: @@
 __TOC__
 </StructureSection>
-[[Category: Koag, M C.]]
+[[Category: Koag, M C]]
-[[Category: Lee, S.]]
+[[Category: Lee, S]]
 [[Category: Human dna polymerase beta]]

4pha

From Proteopedia

Revision as of 00:25, 25 December 2014

Structure of human DNA polymerase beta complexed with A in the template base paired with incoming non-hydrolyzable CTP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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