1-Amino-2-imidazol-4'-ylethylphosphonic acid is a potent reversible inhibitor of Pseudomonas putida histidine ammonia-lyase

A phosphonic acid analogue of L-histidine, 1-amino-2-imidazol-4'-ylethylphosphonic acid (HisP), was identified as a reversible competitive inhibitor of histidine ammonia-lyase (histidase). The affinity of histidase for HisP was pH dependent, with Ki values of 0.28 microM and 10.4 microM compared to substrate Km values of 1 and 5 mM at pH 7 and 9, respectively. HisP did not appear to be a substrate for histidase. A twenty-fold molar excess of HisP over enzyme completely protected the active site of histidase from inactivation by 10 mM bisulfite. Neither isohistidine nor two other phosphonic acid compounds were inhibitory towards histidase when tested at 1 mM concentration.