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PDBsum entry 3ltp
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References listed in PDB file
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Key reference
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Title
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Conformational changes in orotidine 5'-Monophosphate decarboxylase: "remote" residues that stabilize the active conformation.
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Authors
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B.M.Wood,
T.L.Amyes,
A.A.Fedorov,
E.V.Fedorov,
A.Shabila,
S.C.Almo,
J.P.Richard,
J.A.Gerlt.
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Ref.
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Biochemistry, 2010,
49,
3514-3516.
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PubMed id
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Abstract
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The structural factors responsible for the extraordinary rate enhancement (
approximately 10(17)) of the reaction catalyzed by orotidine 5'-monophosphate
decarboxylase (OMPDC) have not been defined. Catalysis requires a conformational
change that closes an active site loop and "clamps" the orotate base proximal to
hydrogen-bonded networks that destabilize the substrate and stabilize the
intermediate. In the OMPDC from Methanobacter thermoautotrophicus, a "remote"
structurally conserved cluster of hydrophobic residues that includes Val 182 in
the active site loop is assembled in the closed, catalytically active
conformation. Substitution of these residues with Ala decreases k(cat)/K(m) with
a minimal effect on k(cat), providing evidence that the cluster stabilizes the
closed conformation. The intrinsic binding energies of the 5'-phosphate group of
orotidine 5'-monophosphate for the mutant enzymes are similar to that for the
wild type, supporting this conclusion.
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