5tba

From Proteopedia

(Difference between revisions)

Revision as of 07:51, 27 November 2019

Postcatalytic ternary complex of Human DNA Polymerase Beta with Gapped DNA substrate, incorporated (-)3TC and PPi.

Structural highlights

5tba 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:	5tbc, 5tb8, 5tbb, 5tb9
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

DNA polymerases are essential enzymes that faithfully and efficiently replicate genomic information.1-3 The mechanism of nucleotide incorporation by DNA polymerases has been extensively studied structurally and kinetically, but several key steps following phosphodiester bond formation remain structurally uncharacterized due to utilization of natural nucleotides. It is thought that the release of pyrophosphate (PPi) triggers reverse conformational changes in a polymerase in order to complete a full catalytic cycle as well as prepare for DNA translocation and subsequent incorporation events. Here, by using the triphosphates of chain-terminating antiviral drugs lamivudine ((-)3TC-TP) and emtricitabine ((-)FTC-TP), we structurally reveal the correct sequence of post-chemistry steps during nucleotide incorporation by human DNA polymerase beta (hPolbeta) and provide a structural basis for PPi release. These post-catalytic structures reveal hPolbeta in an open conformation with PPi bound in the active site, thereby strongly suggesting that the reverse conformational changes occur prior to PPi release. The results also help to refine the role of the newly discovered third divalent metal ion for DNA polymerase-catalyzed nucleotide incorporation. Furthermore, a post-chemistry structure of hPolbeta in the open conformation, following incorporation of (-)3TC-MP, with a second (-)3TC-TP molecule bound to the active site in the absence of PPi, suggests that nucleotide binding stimulates PPi dissociation and occurs before polymerase translocation. Our structural characterization defines the order of the elusive post-chemistry steps in the canonical mechanism of a DNA polymerase.

Structural Insights into the Post-Chemistry Steps of Nucleotide Incorporation Catalyzed by a DNA Polymerase.,Reed AJ, Vyas R, Raper AT, Suo Z J Am Chem Soc. 2017 Jan 11;139(1):465-471. doi: 10.1021/jacs.6b11258. Epub 2016, Dec 27. PMID:27959534^[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
↑ Reed AJ, Vyas R, Raper AT, Suo Z. Structural Insights into the Post-Chemistry Steps of Nucleotide Incorporation Catalyzed by a DNA Polymerase. J Am Chem Soc. 2017 Jan 11;139(1):465-471. doi: 10.1021/jacs.6b11258. Epub 2016, Dec 27. PMID:27959534 doi:http://dx.doi.org/10.1021/jacs.6b11258

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/5tba"

@@ Line 1: / Line 1: @@
 ==Postcatalytic ternary complex of Human DNA Polymerase Beta with Gapped DNA substrate, incorporated (-)3TC and PPi.==
-<StructureSection load='5tba' size='340' side='right' caption='[[5tba]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
+<StructureSection load='5tba' size='340' side='right'caption='[[5tba]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tba]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TBA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tba]] 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=5TBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TBA FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=42E:[(2R,5S)-5-(4-AMINO-2-OXOPYRIMIDIN-1(2H)-YL)-1,3-OXATHIOLAN-2-YL]METHYL+DIHYDROGEN+PHOSPHATE'>42E</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PPV:PYROPHOSPHATE'>PPV</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tbc|5tbc]], [[5tb8|5tb8]], [[5tbb|5tbb]], [[5tb9|5tb9]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLB ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tba OCA], [http://pdbe.org/5tba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tba RCSB], [http://www.ebi.ac.uk/pdbsum/5tba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tba ProSAT]</span></td></tr>
 </table>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5tba" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Suo, Z]]
 [[Category: Vyas, R]]

5tba

From Proteopedia

Revision as of 07:51, 27 November 2019

Postcatalytic ternary complex of Human DNA Polymerase Beta with Gapped DNA substrate, incorporated (-)3TC and PPi.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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