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Inhibition of Histidine Ammonia Lyase by Heteroaryl‐alanines and Acrylates
Author(s) -
Katona Adrian,
Toşa Monica Ioana,
Paizs Csaba,
Rétey János
Publication year - 2006
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200690053
Subject(s) - chemistry , histidine , stereochemistry , imidazole , ammonia , substrate (aquarium) , glycine , lyase , active site , medicinal chemistry , enzyme , organic chemistry , amino acid , biochemistry , geology , oceanography
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 β ‐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 μ M . 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‐1 H ‐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 m M which is to be compared with the K m value of 15.6 m M for the normal reaction. We conclude that 5‐methyl‐1 H ‐imidazole and glycine mimic the substrate and occupy the active site of HAL in a similar orientation.