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Communication

Conversion of Homocysteine to Methionine by Methionine Synthase: A Density Functional Study

Supporting Info

Kasper P. Jensen and Ulf Ryde*

Department of Theoretical Chemistry, Lund University, Chemical Center, P.O. Box 124, S-221 00 Lund, Sweden

J. Am. Chem. Soc., 2003, 125 (46), pp 13970–13971

DOI: 10.1021/ja034697a

Publication Date (Web): October 24, 2003

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

Ulf.Ryde@teokem.lu.se

Abstract

This communication reports a theoretical study of the conversion of homocysteine to methionine by methionine synthase. The reaction pathway is based on density functional calculations with large basis sets, including thermodynamic, relativistic, and solvent effects. We find that the suggested S_N2 mechanism explains well the experimentally observed reaction rate. The results show that the reaction is highly polar, as reflected in the change of charge density along the reaction coordinate. It is enhanced in the protein by two effects: deprotonation of the bound substrate and desolvation of substrate and cofactor in the rate-determining step.

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