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PDBsum entry 2eug
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of escherichia coli uracil DNA glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited.
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Authors
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G.Xiao,
M.Tordova,
J.Jagadeesh,
A.C.Drohat,
J.T.Stivers,
G.L.Gilliland.
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Ref.
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Proteins, 1999,
35,
13-24.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 7.
Figure 7. Hypothetical oxycarbenium-ion transition-state for
glycosidic bond hydrolysis in DNA.
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Figure 8.
Figure 8. Pyrrolidine-based transition-state analog for DNA
glycosylases.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(1999,
35,
13-24)
copyright 1999.
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