title: Quantum mechanical study of the intermediates formed following the reaction of the histidine decarboxylase's substrate and inhibitors with coenzyme.
abstract: Histidine decarboxylase catalyses the decarboxylation of l-histidine to histamine using pyridoxal-5'-phosphate (PLP) as coenzyme. The PM3 quantum mechanical conformation method of analysis and heat of formation calculation were carried out for intermediates which are probably formed during the interaction of histidine (substrate), (s)-alpha-methylhistidine, (s)-alpha-hydrazinohistidine, (s)-alpha-fluoromethylhistidine and (s)-alpha-difluoromethylhistidine (inhibitors) with PLP-dependent histidine decarboxylase from Morganella morganii. The results suggest that the structures of the intermediates before and after decarboxylation were found to exist in a conformation showing a planar arrangement of the double bonds with the pyridoxylidene ring and the bond to the carboxyl group being perpendicular to this plane. After decarboxylation, all the double bonds are in the plane of the pyridoxylidene ring which facilitates the electron displacement for the following protonation at C(alpha). The values of the enthalpy for intermediates would increase the probability of their formation in the enzyme's active site which are consistent with all available stereochemical and mechanistic data.
authors.affiliation: Deptartment of Pharmacology, Baghiyatollah University Medical Sciences, P.O. Box 19585-698, Tehran, Iran. Taha@genetic.nrcgeb.ac.ir
authors.forename: F S
authors.initials: FS
authors.lastname: Tahanejad
authors.forename: H
authors.initials: H
authors.lastname: Naderi-Manesh
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D003067:Coenzymes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006639:Histidine / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011732:Pyridoxal Phosphate / Q000378:metabolism; D011789:Quantum Theory
chemical_list: D003067:Coenzymes; D004791:Enzyme Inhibitors; D006639:Histidine; D011732:Pyridoxal Phosphate; D006640:Histidine Decarboxylase