Structural studies on bio-active compounds. Part 11. Molecular modelling, crystallographic, and biochemical studies of the interactions of (±)-α-vinylserine with the enzyme serine hydroxymethyltransferase

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Abstract
(±)-α-Vinylserine has previously been found to be a competitive inhibitor of serine hydroxymethyltransferase, an important target in anti-tumour chemotherapy. The crystal structure of (±)-α-vinylserine was determined by X-ray diffraction techniques, and molecular modelling was used to build the amino acid pyridoxal 5′-monophosphate Schiff's base. Molecular-mechanics calculations indicate that the reacting conformation for the cleavage of the α–β bond of the compound when bound to pyridoxal 5′-monophosphate is achievable. However, this compound, when incubated with homogeneous rabbit-liver serine hydroxymethyltransferase, was not dehydroxymethylated under any conditions, nor could any quinonoid intermediates be detected. Circular dichroism spectroscopy indicates that this molecule is not an effective enzyme inhibitor because it is not forming an imine base with the pyridoxal phosphate at the active site of the enzyme.

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