title: Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one.
abstract: Previously it was found that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. Here 3-chloro-1-(4-hydroxyphenyl)propan-1-one (9), a 4-hydroxybenzaldehyde analogue, was found to inactivate potently the enzyme in a time-dependent manner. alpha-Ketoglutarate prevented the enzyme from inactivation, suggesting that the inactivation occurs in its active site. Several experiments indicated that the inactivation is irreversible. This study provides a novel strategy for the design of more effective inhibitors.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China.
authors.forename: Yun-Hai
authors.initials: YH
authors.lastname: Tao
authors.forename: Hui-Bi
authors.initials: HB
authors.lastname: Xu
authors.forename: Xiang-Liang
authors.initials: XL
authors.lastname: Yang
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007656:Ketoglutaric Acids / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D011427:Propiophenones / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: C539881:3-chloro-1-(4-hydroxyphenyl)propan-1-one; D004791:Enzyme Inhibitors; D007656:Ketoglutaric Acids; D011427:Propiophenones; D000612:4-Aminobutyrate Transaminase