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|7icl, resolution 3.10Å ()|
|Related:||7ice, 7icf, 7icg, 7ich, 7ici, 7icj, 7ick, 7icm, 7icn, 7ico, 7icp, 7icq, 7icr, 7ics, 7ict, 7icu, 7icv, 8ica, 8icb, 8icc, 8ice, 8icf, 8icg, 8ich, 8ici, 8icj, 8ick, 8icl, 8icm, 8icn, 8ico, 8icp, 8icq, 8icr, 8ics, 8ict, 8icu, 8icv, 8icw, 8icx, 8icy, 8icz, 9ica, 9icb, 9icc, 9ice, 9icf, 9icg, 9ich, 9ici, 9icj, 9ick, 9icl, 9icm, 9icn, 9ico, 9icp, 9icq, 9icr, 9ics, 9ict, 9icu, 9icv, 9icw, 9icx, 9icy, 1zqa, 1zqb, 1zqc, 1zqd, 1zqe, 1zqf, 1zqg, 1zqh, 1zqi, 1zqj, 1zqk, 1zql, 1zqm, 1zqn, 1zqo, 1zqp, 1zqq, 1zqr, 1zqs, 1zqt|
DNA POLYMERASE BETA (POL B) (E.C.188.8.131.52) COMPLEXED WITH SIX BASE PAIRS OF DNA; SOAKED IN THE PRESENCE OF MNCL2 (0.1 MILLIMOLAR)
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.