title: Characterization of novel imidazole derivative, JM-8686, a potent inhibitor of allene oxide synthase.
abstract: The inhibitory properties of a first synthetic jasmonic acid biosynthesis inhibitor, JM-8686, were investigated. Steady-state kinetic analysis indicates that the compound is a competitive inhibitor of allene oxide synthase (AOS) with a K(i) value of approximate 0.62+/-0.15 microM. Dialysis experiment indicates that AOS inactivation by JM-8686 is reversible. The optical difference spectroscopy analysis of JM-8686 and AOS interaction indicates that JM-8686 induced type II binding spectra with a K(d) value of approximate 1.6+/-0.2 microM, suggesting that JM-8686 binds to the prosthetic heme iron of AOS. Comparison of the inhibitory potency of the compound against HPL (CYP74B) from tomato revealed that JM-8686 was a highly selective inhibitor for AOS.
authors.affiliation: Department of Biotechnology, Faculty of Bio-resource Sciences, Akita Prefectural University, Akita 010-0195, Japan. jmwang@akita-pu.ac.jp
authors.forename: Keimei
authors.initials: K
authors.lastname: Oh
authors.forename: Tadao
authors.initials: T
authors.lastname: Asami
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsui
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Howe
authors.forename: Noboru
authors.initials: N
authors.lastname: Murofushi
mesh_terms: D017360:Arabidopsis / Q000187:drug effects / Q000201:enzymology; D002210:Caprylates / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007700:Kinetics; D015394:Molecular Structure; D011485:Protein Binding
chemical_list: C515148:8-(1-(2,4-dichlorophenyl)-2-imidazol-1-ylethoxy)octanoic acid heptyl ester; D002210:Caprylates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019746:Intramolecular Oxidoreductases; C021377:hydroperoxide isomerase