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

A 'remote' structurally conserved cluster of hydrophobic residues in the OMPDC from Methanobacter thermoautotrophicus that includes Val 182 in the active site loop assembled in the closed, catalytically active conformation is reported. Substitution of the cluster of hydrophobic residues with Ala decreases [k.sub.cat]/[K.sub.m] with a minimal effect on [k.sub.cat] provides evidence that the cluster stabilizes the closed conformation.