4o5c

From Proteopedia

(Difference between revisions)

Revision as of 17:20, 9 March 2017

Structure of human DNA polymerase complexed with N7-MG as the template base in a 1-nucleotide gapped DNA

Structural highlights

4o5c is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	3isb, 1bpx, 4o5e, 4o5k
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

N7-Methyl-2'-deoxyguanosine (m7dG) is the predominant lesion formed by methylating agents. A systematic investigation on the effect of m7dG on DNA replication has been difficult due to the chemical instability of m7dG. To gain insights into the m7dG effect, we employed a 2'-fluorine-mediated transition-state destabilzation strategy. Specifically, we determined kinetic parameters for dCTP insertion opposite a chemically stable m7dG analogue, 2'-fluoro-m7dG (Fm7dG), by human DNA polymerase beta (polbeta) and solved three X-ray structures of polbeta in complex with the templating Fm7dG paired with incoming dCTP or dTTP analogues. The kinetic studies reveal that the templating Fm7dG slows polbeta catalysis approximately 300-fold, suggesting that m7dG in genomic DNA may impede replication by some DNA polymerases. The structural analysis reveals that Fm7dG forms a canonical Watson-Crick base pair with dCTP, but metal ion coordination is suboptimal for catalysis in the polbeta-Fm7dG:dCTP complex, which partially explains the slow insertion of dCTP opposite Fm7dG by polbeta. In addition, the polbeta-Fm7dG:dTTP structure shows open protein conformations and staggered base pair conformations, indicating that N7-methylation of dG does not promote a promutagenic replication. Overall, the first systematic studies on the effect of m7dG on DNA replication reveal that polbeta catalysis across m7dG is slow, yet highly accurate.

Transition-state destabilization reveals how human DNA polymerase beta proceeds across the chemically unstable lesion N7-methylguanine.,Koag MC, Kou Y, Ouzon-Shubeita H, Lee S Nucleic Acids Res. 2014 Jun 25. pii: gku554. PMID:24966350^[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, Kou Y, Ouzon-Shubeita H, Lee S. Transition-state destabilization reveals how human DNA polymerase beta proceeds across the chemically unstable lesion N7-methylguanine. Nucleic Acids Res. 2014 Jun 25. pii: gku554. PMID:24966350 doi:http://dx.doi.org/10.1093/nar/gku554

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o5c"

@@ Line 1: / Line 1: @@
 ==Structure of human DNA polymerase complexed with N7-MG as the template base in a 1-nucleotide gapped DNA==
 <StructureSection load='4o5c' size='340' side='right' caption='[[4o5c]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMG:2-AMINO-9-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-7-METHYL-6-OXO-6,9-DIHYDRO-1H-PURIN-7-IUM'>FMG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3isb|3isb]], [[1bpx|1bpx]], [[4o5e|4o5e]], [[4o5k|4o5k]]</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=4o5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o5c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o5c RCSB], [http://www.ebi.ac.uk/pdbsum/4o5c PDBsum]</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=4o5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o5c OCA], [http://pdbe.org/4o5c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o5c RCSB], [http://www.ebi.ac.uk/pdbsum/4o5c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o5c ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4o5c" style="background-color:#fffaf0;"></div>
 ==See Also==

4o5c

From Proteopedia

Revision as of 17:20, 9 March 2017

Structure of human DNA polymerase complexed with N7-MG as the template base in a 1-nucleotide gapped DNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox