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[[Image: | ==DNA POLYMERASE BETA (POL B) (E.C.2.7.7.7) COMPLEXED WITH SIX BASE PAIRS OF DNA; SOAKED IN THE PRESENCE OF MNCL2 (0.1 MILLIMOLAR) AND IN THE ABSENCE OF NACL== | ||
<StructureSection load='7icv' size='340' side='right' caption='[[7icv]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7icv]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ICV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7ICV 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">[[7ice|7ice]], [[7icf|7icf]], [[7icg|7icg]], [[7ich|7ich]], [[7ici|7ici]], [[7icj|7icj]], [[7ick|7ick]], [[7icl|7icl]], [[7icm|7icm]], [[7icn|7icn]], [[7ico|7ico]], [[7icp|7icp]], [[7icq|7icq]], [[7icr|7icr]], [[7ics|7ics]], [[7ict|7ict]], [[7icu|7icu]], [[8ica|8ica]], [[8icb|8icb]], [[8icc|8icc]], [[8ice|8ice]], [[8icf|8icf]], [[8icg|8icg]], [[8ich|8ich]], [[8ici|8ici]], [[8icj|8icj]], [[8ick|8ick]], [[8icl|8icl]], [[8icm|8icm]], [[8icn|8icn]], [[8ico|8ico]], [[8icp|8icp]], [[8icq|8icq]], [[8icr|8icr]], [[8ics|8ics]], [[8ict|8ict]], [[8icu|8icu]], [[8icv|8icv]], [[8icw|8icw]], [[8icx|8icx]], [[8icy|8icy]], [[8icz|8icz]], [[9ica|9ica]], [[9icb|9icb]], [[9icc|9icc]], [[9ice|9ice]], [[9icf|9icf]], [[9icg|9icg]], [[9ich|9ich]], [[9ici|9ici]], [[9icj|9icj]], [[9ick|9ick]], [[9icl|9icl]], [[9icm|9icm]], [[9icn|9icn]], [[9ico|9ico]], [[9icp|9icp]], [[9icq|9icq]], [[9icr|9icr]], [[9ics|9ics]], [[9ict|9ict]], [[9icu|9icu]], [[9icv|9icv]], [[9icw|9icw]], [[9icx|9icx]], [[9icy|9icy]], [[1zqa|1zqa]], [[1zqb|1zqb]], [[1zqc|1zqc]], [[1zqd|1zqd]], [[1zqe|1zqe]], [[1zqf|1zqf]], [[1zqg|1zqg]], [[1zqh|1zqh]], [[1zqi|1zqi]], [[1zqj|1zqj]], [[1zqk|1zqk]], [[1zql|1zql]], [[1zqm|1zqm]], [[1zqn|1zqn]], [[1zqo|1zqo]], [[1zqp|1zqp]], [[1zqq|1zqq]], [[1zqr|1zqr]], [[1zqs|1zqs]], [[1zqt|1zqt]]</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=7icv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7icv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=7icv RCSB], [http://www.ebi.ac.uk/pdbsum/7icv PDBsum]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ic/7icv_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
When crystals of human DNA polymerase beta (pol beta) complexed with DNA [Pelletier, H., Sawaya, M. R., Wolfle, W., Wilson, S. H., & Kraut, J. (1996) Biochemistry 35, 12742-12761] are soaked in the presence of dATP and Mn2+, X-ray structural analysis shows that nucleotidyl transfer to the primer 3'-OH takes place directly in the crystals, even though the DNA is blunt-ended at the active site. Under similar crystal-soaking conditions, there is no evidence for a reaction when Mn2+ is replaced by Mg2+, which is thought to be the divalent metal ion utilized by most polymerases in vivo. These results suggest that one way Mn2+ may manifest its mutagenic effect on polymerases is by promoting greater reactivity than Mg2+ at the catalytic site, thereby allowing the nucleotidyl transfer reaction to take place with little or no regard to instructions from a template. Non-template-directed nucleotidyl transfer is also observed when pol beta-DNA cocrystals are soaked in the presence of dATP and Zn2+, but the reaction products differ in that the sugar moiety of the incorporated nucleotide appears distorted or otherwise cleaved, in agreement with reports that Zn2+ may act as a polymerase inhibitor rather than as a mutagen [Sirover, M. A., & Loeb, L. A. (1976) Science 194, 1434-1436]. Although no reaction is observed when crystals are soaked in the presence of dATP and other metal ions such as Ca2+, Co2+, Cr3+, or Ni2+, X-ray structural analyses show that these metal ions coordinate the triphosphate moiety of the nucleotide in a manner that differs from that observed with Mg2+. In addition, all metal ions tested, with the exception of Mg2+, promote a change in the side-chain position of aspartic acid 192, which is one of three highly conserved active-site carboxylate residues. Soaking experiments with nucleotides other than dATP (namely, dCTP, dGTP, dTTP, ATP, ddATP, ddCTP, AZT-TP, and dATP alpha S) reveal a non-base-specific binding site on pol beta for the triphosphate and sugar moieties of a nucleotide, suggesting a possible mechanism for nucleotide selectivity whereby triphosphate-sugar binding precedes a check for correct base pairing with the template. | |||
A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta.,Pelletier H, Sawaya MR, Wolfle W, Wilson SH, Kraut J Biochemistry. 1996 Oct 1;35(39):12762-77. PMID:8841119<ref>PMID:8841119</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[DNA polymerase|DNA polymerase]] | *[[DNA polymerase|DNA polymerase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Pelletier, H | [[Category: Pelletier, H]] | ||
[[Category: Sawaya, M R | [[Category: Sawaya, M R]] | ||
[[Category: Dna repair]] | [[Category: Dna repair]] | ||
[[Category: Dna replication]] | [[Category: Dna replication]] | ||