3eug
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CRYSTAL STRUCTURE OF ESCHERICHIA COLI URACIL DNA GLYCOSYLASE AND ITS COMPLEXES WITH URACIL AND GLYCEROL: STRUCTURE AND GLYCOSYLASE MECHANISM REVISITED
OverviewOverview
The DNA repair enzyme uracil DNA glycosylase (UDG) catalyzes the, hydrolysis of premutagenic uracil residues from single-stranded or duplex, DNA, producing free uracil and abasic DNA. Here we report the, high-resolution crystal structures of free UDG from Escherichia coli, strain B (1.60 A), its complex with uracil (1.50 A), and a second, active-site complex with glycerol (1.43 A). These represent the first, high-resolution structures of a prokaryotic UDG to be reported. The, overall structure of the E. coli enzyme is more similar to the human UDG, than the herpes virus enzyme. Significant differences between the, bacterial and viral structures are seen in the side-chain positions of the, putative general-acid (His187) and base (Asp64), similar to differences, previously observed between the viral and human enzymes. In general, the, active-site loop that contains His187 appears preorganized in comparison, with the viral and human enzymes, requiring smaller substrate-induced, conformational changes to bring active-site groups into catalytic, position. These structural differences may be related to the large, differences in the mechanism of uracil recognition used by the E. coli and, viral enzymes. The pH dependence of k(cat) for wild-type UDG and the D64N, and H187Q mutant enzymes is consistent with general-base catalysis by, Asp64, but provides no evidence for a general-acid catalyst. The catalytic, mechanism of UDG is critically discussed with respect to these results.
About this StructureAbout this Structure
3EUG is a Single protein structure of sequence from Escherichia coli with GOL as ligand. Active as Uridine nucleosidase, with EC number 3.2.2.3 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of Escherichia coli uracil DNA glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited., Xiao G, Tordova M, Jagadeesh J, Drohat AC, Stivers JT, Gilliland GL, Proteins. 1999 Apr 1;35(1):13-24. PMID:10090282
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