5u8h

From Proteopedia

(Difference between revisions)

Revision as of 13:52, 27 April 2017

DNA Polymerase Beta G231D crystallized in PEG 400

Structural highlights

5u8h is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5u8i, 5u8g
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

With the formidable growth in the volume of genetic information, it has become essential to identify and characterize mutations in macromolecules not only to predict contributions to disease processes but also to guide the design of therapeutic strategies. While mutations of certain residues have a predictable phenotype based on their chemical nature and known structural position, many types of mutations evade prediction based on current information. Described in this work are the crystal structures of two cancer variants located in the palm domain of DNA polymerase beta (pol beta), S229L and G231D, whose biological phenotype was not readily linked to a predictable structural implication. Structural results demonstrate that the mutations elicit their effect through subtle influences on secondary interactions with a residue neighboring the active site. Residues 229 and 231 are 7.5 and 12.5 A, respectively, from the nearest active site residue, with a beta-strand between them. A residue on this intervening strand, M236, appears to transmit fine structural perturbations to the catalytic metal-coordinating residue D256, affecting its conformational stability.

Remote Mutations Induce Functional Changes in Active Site Residues of Human DNA Polymerase beta.,Eckenroth BE, Towle-Weicksel JB, Nemec AA, Murphy DL, Sweasy JB, Doublie S Biochemistry. 2017 Apr 21. doi: 10.1021/acs.biochem.6b01287. PMID:28402631^[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
↑ Eckenroth BE, Towle-Weicksel JB, Nemec AA, Murphy DL, Sweasy JB, Doublie S. Remote Mutations Induce Functional Changes in Active Site Residues of Human DNA Polymerase beta. Biochemistry. 2017 Apr 21. doi: 10.1021/acs.biochem.6b01287. PMID:28402631 doi:http://dx.doi.org/10.1021/acs.biochem.6b01287

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/5u8h"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5u8h is ON HOLD  until Paper Publication
+==DNA Polymerase Beta G231D crystallized in PEG 400==
+<StructureSection load='5u8h' size='340' side='right' caption='[[5u8h]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5u8h]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U8H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U8H FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u8i|5u8i]], [[5u8g|5u8g]]</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=5u8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8h OCA], [http://pdbe.org/5u8h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u8h RCSB], [http://www.ebi.ac.uk/pdbsum/5u8h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8h ProSAT]</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 ==
+With the formidable growth in the volume of genetic information, it has become essential to identify and characterize mutations in macromolecules not only to predict contributions to disease processes but also to guide the design of therapeutic strategies. While mutations of certain residues have a predictable phenotype based on their chemical nature and known structural position, many types of mutations evade prediction based on current information. Described in this work are the crystal structures of two cancer variants located in the palm domain of DNA polymerase beta (pol beta), S229L and G231D, whose biological phenotype was not readily linked to a predictable structural implication. Structural results demonstrate that the mutations elicit their effect through subtle influences on secondary interactions with a residue neighboring the active site. Residues 229 and 231 are 7.5 and 12.5 A, respectively, from the nearest active site residue, with a beta-strand between them. A residue on this intervening strand, M236, appears to transmit fine structural perturbations to the catalytic metal-coordinating residue D256, affecting its conformational stability.
-Authors: Eckenroth, B.E., Doublie, S.
+Remote Mutations Induce Functional Changes in Active Site Residues of Human DNA Polymerase beta.,Eckenroth BE, Towle-Weicksel JB, Nemec AA, Murphy DL, Sweasy JB, Doublie S Biochemistry. 2017 Apr 21. doi: 10.1021/acs.biochem.6b01287. PMID:28402631<ref>PMID:28402631</ref>
-Description: DNA Polymerase Beta G231D crystallized in PEG 400
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Eckenroth, B.E]]
+<div class="pdbe-citations 5u8h" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Doublie, S]]
+[[Category: Eckenroth, B E]]
+[[Category: Dna complex]]
+[[Category: Dna polymerase]]
+[[Category: Lyase]]
+[[Category: Lyase-dna complex]]
+[[Category: Transferase]]

5u8h

From Proteopedia

Revision as of 13:52, 27 April 2017

DNA Polymerase Beta G231D crystallized in PEG 400

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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