Conformational changes in orotidine 5'-monophosphate decarboxylase: "remote" residues that stabilize the active conformation.

ABSTRACT: 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. T

SUBMITTER: Wood BM 

PROVIDER: S-EPMC3245974 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature