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PDBsum entry 1ak5
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Oxidoreductase
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PDB id
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1ak5
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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 tritrichomonas foetus inosine-5'-Monophosphate dehydrogenase and the enzyme-Product complex.
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Authors
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F.G.Whitby,
H.Luecke,
P.Kuhn,
J.R.Somoza,
J.A.Huete-Perez,
J.D.Phillips,
C.P.Hill,
R.J.Fletterick,
C.C.Wang.
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Ref.
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Biochemistry, 1997,
36,
10666-10674.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
0%.
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Abstract
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Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for
the control of parasitic infections. The enzyme catalyzes the oxidation of
inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed
step in de novo guanosine monophosphate (GMP) biosynthesis. We have determined
the crystal structures of IMPDH from the protozoan parasite Tritrichomonas
foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A
resolution. Each monomer of this tetrameric enzyme is comprised of two domains,
the largest of which includes an eight-stranded parallel beta/alpha-barrel that
contains the enzyme active site at the C termini of the barrel beta-strands. A
second domain, comprised of residues 102-220, is disordered in the crystal.
IMPDH is expected to be active as a tetramer, since the active site cavity is
formed by strands from adjacent subunits. An intrasubunit disulfide bond, seen
in the crystal structure, may stabilize the protein in a less active form, as
high concentrations of reducing agent have been shown to increase enzyme
activity. Disorder at the active site suggests that a high degree of flexibility
may be inherent in the catalytic function of IMPDH. Unlike IMPDH from other
species, the T. foetus enzyme has a single arginine that is largely responsible
for coordinating the substrate phosphate in the active site. This structural
uniqueness may facilitate structure-based identification and design of compounds
that specifically inhibit the parasite enzyme.
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