Reaction of Lactobacillus histidine decarboxylase with L-histidine methyl ester.
L-Histidine methyl ester inactivates histidine decarboxylase in a time-dependent manner. The possibility was considered that an irreversible reaction between enzyme and inhibitor occurs [Recsei, P. A., & Snell, E. E. (1970) Biochemistry 9, 1492-1497]. We have confirmed time-dependent inactivation by histidine methyl ester and have investigated the structure of the enzyme-inhibitor complex. Upon exposure to either 8 M guanidinium chloride or 6% trichloroacetic acid, unchanged histidine methyl ester is recovered. Formation of the complex involves Schiff base formation, most likely with the active site pyruvyl residue [Huynh, Q. K., & Snell, E. E. (1986) J. Biol. Chem. 261, 4389-4394], but does not involve additional irreversible covalent interaction between inhibitor and enzyme. Complex formation is a two-step process involving rapidly reversible formation of a loose complex and essentially irreversible formation of a tight complex. For the formation of the tight complex, Ki = 80 nM and koff = 2.5 X 10(-4) min-1. Time-dependent inhibition was also observed with L-histidine ethyl ester, L-histidinamide, and DL-3-amino-4-(4-imidazolyl)-2-butanone. No inactivation was observed with glycine methyl ester or histamine. We propose that in the catalytic reaction the carboxyl group of the substrate is in a hydrophobic region. The unfavorable interaction between the carboxylate group and the hydrophobic region facilitates decarboxylation [Crosby, J., Stone, R., & Liehard, G. E. (1970) J. Am. Chem. Soc. 92, 2891-2900]. With histidine methyl ester this unfavorable interaction is no longer present; hence, there is tight binding.(ABSTRACT TRUNCATED AT 250 WORDS)
D001665:Binding Sites; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006639:Histidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007778:Lactobacillus / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D004791:Enzyme Inhibitors; D006639:Histidine; C053861:histidine methyl ester; D002262:Carboxy-Lyases; D006640:Histidine Decarboxylase