Wild-type enzyme ODCase

Fig. 1 Computed free energy reaction profiles for the decarboxylation of OMP in water and in the wild-type enzyme ODCase. Reprinted with permission from Reference 66. Copyright 2000 National Academy of Sciences.

The relative contribution of each interaction was calculated from the ratio of the ligand dissociation constant determined with the mutant enzyme to that determined with wild-type yeast ODCase... 

The mechanism of the enzymatic decarboxylation of orotidine 5 -mono-phosphate (OMP) to uridine 5 -monophosphate (UMP) (see Fig. 1) is an intriguing problem for which many solutions have been offered. Even before 1995 when Wolfenden and Radzicka declared OMP decarboxylase (ODCase) to be the most proficient enzyme [1], several different mechanisms had been proposed. Since that time, other mechanisms have been advocated. Curiously, the appearance of crystal structures for various wild-type and mutant ODCases has led not to a definitive picture of catalysis, but to even more conjecture and controversy concerning the mechanism. 

Wu and Pai provide a thorough examination of the molecular structure of ODCase, based on X-ray crystallographic studies of wild-type and mutant ODCases bound with various inhibitors. The implications of these structural studies are discussed, with an emphasis on the possibility that the conformational dynamics of the enzyme may be the key to catalysis. 

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