3rh5: Difference between revisions
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[[ | ==DNA Polymerase Beta Mutant (Y271) with a dideoxy-terminated primer with an incoming deoxynucleotide (dCTP)== | ||
<StructureSection load='3rh5' size='340' side='right' caption='[[3rh5]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3rh5]] is a 4 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=3RH5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RH5 FirstGlance]. <br> | |||
</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=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rh4|3rh4]], [[3rh6|3rh6]]</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 Homo sapiens])</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=3rh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rh5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rh5 RCSB], [http://www.ebi.ac.uk/pdbsum/3rh5 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DNA polymerases can misinsert ribonucleotides that lead to genomic instability. DNA polymerase beta discourages ribonucleotide insertion with the backbone carbonyl of Tyr-271; alanine substitution of Tyr-271, but not Phe-272, resulted in a > 10-fold loss in discrimination. The Y271A mutant also inserted ribonucleotides more efficiently than wild type on a variety of rNMP-containing DNA substrates. Substituting Mn(2+) for Mg(2+) decreased sugar discrimination for both wild-type and mutant enzymes primarily by increasing the affinity for rCTP. This facilitated crystallization of ternary substrate complexes of both the wild-type and Y271A mutant enzymes. Crystallographic structures of Y271A- and wild type-substrate complexes indicate that rCTP is well accommodated in the active site, but that O2' of rCTP and the carbonyl oxygen of Tyr-271 or Ala-271 are unusually close (~2.5 and 2.6 A, respectively). Structure-based modeling indicates that the local energetic cost of positioning these closely spaced oxygens is ~2.2 kcal/mol for the wild-type enzyme. Since the side chain of Tyr-271 also hydrogen bonds with the primer terminus, loss of this interaction affects its catalytic positioning. Our results support a model where DNA polymerase beta utilizes two strategies, steric and geometric, with a single protein residue to deter ribonucleotide insertion. | |||
Molecular insights into DNA polymerase deterrents for Ribonucleotide insertion.,Cavanaugh NA, Beard WA, Batra VK, Perera L, Pedersen LG, Wilson SH J Biol Chem. 2011 Jul 6. PMID:21733843<ref>PMID:21733843</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: Batra, V K | [[Category: Batra, V K]] | ||
[[Category: Beard, W A | [[Category: Beard, W A]] | ||
[[Category: Cavanaugh, N A | [[Category: Cavanaugh, N A]] | ||
[[Category: Pedersen, L G | [[Category: Pedersen, L G]] | ||
[[Category: Perera, L | [[Category: Perera, L]] | ||
[[Category: Wilson, S H | [[Category: Wilson, S H]] | ||
[[Category: Dctp]] | [[Category: Dctp]] | ||
[[Category: Dna polymerase beta mutant]] | [[Category: Dna polymerase beta mutant]] | ||