Orotidine monophosphate decarboxylase the mechanism

Orbital interactions and long-range electron transfer, 38, 1 Organic materials for second-order non-linear optics, 32, 121 Organic reactivity, electron-transfer paradigm for, 35, 193 Organic reactivity, structure determination of, 35, 67 Orotidine monophosphate decarboxylase, the mechanism of, 38, 183... 

Orotidine monophosphate decarboxylase, the mechanism of, 38, 183 Oxyacids of sulfur and their anhydrides, mechanisms and reactivity in reactions of organic, 17, 65 Oxygen isotope exchange reactions of organic compounds, 3, 123... 

Computational studies of alkene oxidation reactions by metal-oxo compounds, 38, 131 Computational studies on the mechanism of orotidine monophosphate decarboxylase,... 

Houk KN, Tantillo DJ, Stanton C, Hu Y (2004) What have Theory and Crystallography Revealed About the Mechanism of Catalysis by Orotidine Monophosphate Decarboxylase 238 1-22 Houseman BT, Mrksich M (2002) Model Systems for Studying Polyvalent Carbohydrate Binding Interactions. 218 1-44 Hricoviniovd Z, see Petrus L (2001) 215 15-41 Hu Y, see Houk KN (2004) 238 1-22... 

Lee, J.K. and Houk, K.N. (1997) A proficient enzyme revisited the predicted mechanism for orotidine monophosphate decarboxylase. Science, 276, 942. 

Computational Studies on the Mechanism of Orotidine Monophosphate Decarboxylase... 

Computational studies on the mechanism of orotidine monophosphate decarboxylase 03MI78. 

Orotidine S -monophosphate decarboxylase (ODCase) is a key enzyme in the biosynthesis of nucleic acids, effecting the decarboxylation of orotidine 5 -monophosphate (OMP, 1) to form uridine S -monophosphate (UMP, 2, Scheme l).1,2 The conversion of OMP to UMP is biomechanistically intriguing, because the decarboxylation appears to result, uniquely, in a carbanion (3, mechanism i, Scheme 2) that cannot delocalize into a it orbital.3,4 The uncatalyzed reaction in solution is therefore extremely unfavorable, with a AG of... 

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. 

This article summarizes the mechanistic, crystallographic, and computational evidence for the mechanism of decarboxylation of OMP by the family of orotidine 5 -monophosphate decarboxylase enzymes, and offers a critical evaluation of the various mechanisms based upon this evidence. 

Abstract An energy decomposition scheme is presented to elucidate the importance of the change of protein conformation substates to the reduction of activation barrier in an enzyme-catalyzed reaction. The analysis is illustrated by the reaction of orotidine 5 -monophosphate decarboxylase (ODCase), in which the catalyzed reaction is at least 10 faster than the spontaneous reaction. Analysis reveals that the enzyme conformation is more distorted in the reactant state than in the transition state. The energy released from conformational relaxation of the protein is the main source of the rate enhancement. The proposed mechanism is consistent with results from site-directed mutagenesis where mutations remote from the reaction center affect kcat but not Kyi. 

Stanton CL et al (2007) QM/MM metadynamics study of the direct decarboxylation mechanism for orotidine-5-monophosphate decarboxylase using two different QM regions acceleration too small to explain rate of enzyme catalysis. J Phys Chem B 111 12573-12581... 

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