Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates.

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Katona A, Tosa MI, Paizs C, Retey J

Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates.

Chem Biodivers. 2006 May;3(5):502-8.

PubMed ID

17193285 [ View in PubMed

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Abstract

Histidine ammonia lyase (HAL) catalyzes the elimination of ammonia from the substrate to form (E)-urocanate. The interaction between HAL and acrylic acids or alanines substituted with heteroaryl groups in the beta-position was investigated. These proved to be strong competitive inhibitors when the heteroaryl groups were furanyl, thiophenyl, benzofuranyl, and benzothiophenyl, carrying the alanyl or acrylic side chains either in 2 or 3 positions, with K(i) values between 18 and 139 microM. The exception was (furan-3-yl)alanine which was found to be inert. Tryptophan and 1-methyltryptophan, as well as the corresponding acrylates (=prop-2-enoates), are strong mixed inhibitors of HAL. Theoretically, L-histidine can be dissected into 4-methyl-1H-imidazole and glycine. Whereas these two compounds separately are only very weak inhibitors of HAL, equimolar amounts of both show a K(i) value of 1.7+/-0.09 mM which is to be compared with the K(m) value of 15.6 mM for the normal reaction. We conclude that 5-methyl-1H-imidazole and glycine mimic the substrate and occupy the active site of HAL in a similar orientation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Histidine	Histidine ammonia-lyase	Protein	Humans	Unknown	Not Available	Details