Substrate Distortion Contributes to the Catalysis of Orotidine 5'-Monophosphate Decarboxylase

摘要: Orotidine 5′-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine (OMP) to uridine (UMP) by 17 orders magnitude. Eight new crystal structures with ligand analogues combined computational analyses enzyme’s short-lived intermediates and intrinsic electronic energies distort substrate other ligands improve our understanding still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion its methyl substituent bond, 6-amino-UMP shows competition between K72 C6 substituents for a position close D70, ethyl esters OMP both induce rotation carboxylate group out plane pyrimidine ring. Molecular dynamics quantum mechanics/molecular mechanics computations enzyme–substrate complex also show bond ring be distorted, with...