Methyl transfer in glycine N-methyltransferase. A theoretical study.

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Velichkova P, Himo F

Methyl transfer in glycine N-methyltransferase. A theoretical study.

J Phys Chem B. 2005 Apr 28;109(16):8216-9.

PubMed ID

16851960 [ View in PubMed

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Abstract

Density functional theory calculations using the hybrid functional B3LYP have been performed to study the methyl transfer step in glycine N-methyltransferase (GNMT). This enzyme catalyzes the S-adenosyl-L-methionine (SAM)-dependent methylation of glycine to form sarcosine. The starting point for the calculations is the recent X-ray crystal structure of GNMT complexed with SAM and acetate. Several quantum chemical models with different sizes, employing up to 98 atoms, were used. The calculations demonstrate that the suggested mechanism, where the methyl group is transferred in a single S(N)2 step, is thermodynamically plausible. By adding or eliminating various groups at the active site, it was furthermore demonstrated that hydrogen bonds to the amino group of the glycine substrate lower the reaction barrier, while hydrogen bonds to the carboxylate group raise the barrier.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glycine	Glycine N-methyltransferase	Protein	Humans	Unknown	Substrate	Details