4tuq

From Proteopedia

(Difference between revisions)

Revision as of 08:24, 18 December 2019

Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).

Structural highlights

4tuq is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4tup, 4tur, 4tus
Gene:	POLB (HUMAN)
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

Human DNA polymerase beta (polbeta) has been suggested to play a role in cisplatin resistance, especially in polbeta-overexpressing cancer cells. Polbeta has been shown to accurately, albeit slowly bypass the cisplatin-1,2-d(GpG) (Pt-GG) intramolecular cross-link in vitro. Currently, the structural basis for the inefficient Pt-GG bypass mechanism of polbeta is unknown. To gain structural insights into the mechanism, we determined two ternary structures of polbeta incorporating dCTP opposite the templating Pt-GG lesion in the presence of the active-site Mg2+ or Mn2+. The Mg2+-bound structure shows that the bulky Pt-GG adduct is accommodated in the polbeta active site without any steric hindrance. In addition, both guanines of the Pt-GG lesion form Watson-Crick base pairing with the primer terminus dC and the incoming dCTP, providing the structural basis for the accurate bypass of the Pt-GG adduct by polbeta. The Mn2+-bound structure shows that polbeta adopts a catalytically sub-optimal semi-closed conformation during the insertion of dCTP opposite the templating Pt-GG, explaining the inefficient replication across the Pt-GG lesion by polbeta. Overall, our studies provide the first structural insights into the mechanism of the potential polbeta-mediated cisplatin resistance.

Structural Basis for the Inefficient Nucleotide Incorporation Opposite Cisplatin-DNA Lesion by Human DNA Polymerase beta,Koag MC, Lai L, Lee S J Biol Chem. 2014 Sep 18. pii: jbc.M114.605451. PMID:25237188^[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, Lai L, Lee S. Structural Basis for the Inefficient Nucleotide Incorporation Opposite Cisplatin-DNA Lesion by Human DNA Polymerase beta J Biol Chem. 2014 Sep 18. pii: jbc.M114.605451. PMID:25237188 doi:http://dx.doi.org/10.1074/jbc.M114.605451

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/4tuq"

@@ Line 1: / Line 1: @@
 ==Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).==
-<StructureSection load='4tuq' size='340' side='right' caption='[[4tuq]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
+<StructureSection load='4tuq' size='340' side='right'caption='[[4tuq]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4tuq]] 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=4TUQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TUQ FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4tuq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Koag, M C]]
 [[Category: Lee, S]]

4tuq

From Proteopedia

Revision as of 08:24, 18 December 2019

Human DNA polymerase beta inserting dCMPNPP opposite GG template (GG0b).

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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