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4r65

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==Ternary complex crystal structure of R258A mutant of DNA polymerase Beta==
==Ternary complex crystal structure of R258A mutant of DNA polymerase Beta==
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<StructureSection load='4r65' size='340' side='right' caption='[[4r65]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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<StructureSection load='4r65' size='340' side='right'caption='[[4r65]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4r65]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R65 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4r65]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R65 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r63|4r63]], [[4r64|4r64]], [[4r66|4r66]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<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=4r65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r65 RCSB], [http://www.ebi.ac.uk/pdbsum/4r65 PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r65 OCA], [https://pdbe.org/4r65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r65 RCSB], [https://www.ebi.ac.uk/pdbsum/4r65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r65 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[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>
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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DNA polymerases and substrates undergo conformational changes upon forming protein-ligand complexes. These conformational adjustments can hasten or deter DNA synthesis and influence substrate discrimination. From structural comparison of binary DNA and ternary DNA/dNTP complexes of DNA polymerase beta, several side-chains have been implicated in facilitating formation of an active ternary complex poised for chemistry. Site-directed mutagenesis of these highly conserved residues (Asp192, Arg258, Phe272, Glu295, and Tyr296) and kinetic characterization provides insight into the role these residues play during correct and incorrect insertion as well as their role in conformational activation. The catalytic efficiencies for correct nucleotide insertion for alanine mutants was wild type approximately R258A &gt; F272A approximately Y296A &gt; E295A &gt; D192. Since the efficiencies for incorrect insertion was affected to about the same extent for each mutant, effects on fidelity were modest (&lt;5-fold). The R258A mutant exhibited an increase in the single-turnover rate of correct nucleotide insertion. This suggests that the wild-type Arg258 side-chain generates a population of non-productive ternary complexes. Structures of binary and ternary substrate complexes of the R258A mutant and a mutant associated with gastric carcinomas, E295K, provide molecular insight into intermediate structural conformations not appreciated previously. While the R258A mutant crystal structures were similar to wild-type enzyme, the open ternary complex structure of E295K indicates that Arg258 stabilizes a non-productive conformation of the primer terminus that would decrease catalysis. Significantly, the open E295K ternary complex binds two metal ions indicating that metal binding cannot overcome the modified interactions that have interrupted the closure of the N-subdomain.
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Substrate-Induced DNA Polymerase beta Activation.,Beard WA, Shock DD, Batra VK, Prasad R, Wilson SH J Biol Chem. 2014 Sep 26. pii: jbc.M114.607432. PMID:25261471<ref>PMID:25261471</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Batra, V K]]
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[[Category: Homo sapiens]]
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[[Category: Beard, W A]]
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[[Category: Large Structures]]
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[[Category: Wilson, S H]]
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[[Category: Synthetic construct]]
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[[Category: Conformational change]]
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[[Category: Batra VK]]
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[[Category: Dna polymerase beta]]
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[[Category: Beard WA]]
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[[Category: Enzyme mechanism]]
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[[Category: Wilson SH]]
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[[Category: Transferase-dna complex]]
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Current revision

Ternary complex crystal structure of R258A mutant of DNA polymerase Beta

PDB ID 4r65

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