View source for 9ick

[[Image:9ick.gif|left|200px]]<br />
<applet load="9ick" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="9ick, resolution 2.700&Aring;" />
'''DNA POLYMERASE BETA (E.C.2.7.7.7)/DNA COMPLEX, SOAKED IN THE PRESENCE OF ARTIFICIAL MOTHER LIQUOR'''<br />

==Overview==
When crystals of human DNA polymerase beta (pol beta) complexed with DNA, [Pelletier, H., Sawaya, M. R., Wolfle, W., Wilson, S. H., &amp; 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., &amp; 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.

==About this Structure==
9ICK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=9ICK OCA]. 

==Reference==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8841119 8841119]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Pelletier, H.]]
[[Category: Sawaya, M.R.]]
[[Category: NA]]
[[Category: complex (nucleotidyltransferase/dna)]]
[[Category: dna repair]]
[[Category: dna replication]]
[[Category: dna-directed dna polymerase]]
[[Category: nucleotidyltransferase]]

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