Serine hydroxymethyltransferase revisited.

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Schirch V, Szebenyi DM

Serine hydroxymethyltransferase revisited.

Curr Opin Chem Biol. 2005 Oct;9(5):482-7. doi: 10.1016/j.cbpa.2005.08.017.

PubMed ID

16125438 [ View in PubMed

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Abstract

Recent structural data and the properties of several active site mutants of serine hydroxymethyltransferase have resolved some key questions concerning the catalytic mechanism and broad substrate specificity of this enzyme. In the tetrahydrofolate-dependent conversion of serine to glycine, an early proposed mechanism involved a retroaldol cleavage and a formaldehyde intermediate, while a more recent suggestion posits a direct nucleophilic displacement of the serine hydroxyl by N(5) of tetrahydrofolate, without creation of free formaldehyde. Geometric and chemical difficulties with both options led to a new proposal, a modified retroaldol mechanism in which N(5) of tetrahydrofolate makes a nucleophilic attack on serine C(3) leading to breakage of the C(3)-C(2)-bond of serine rather than the C(3)-hydroxyl bond. Molecular modeling revealed how a variety of substrates could be accommodated in the folate-independent cleavage of 3-hydroxyamino acids and shed light on the mechanism of this reaction.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Levoleucovorin	Serine hydroxymethyltransferase	Protein	Shigella flexneri	Unknown	Not Available	Details