title: Enoyl-CoA hydratase. reaction, mechanism, and inhibition.
abstract: Enoyl-CoA hydratase (ECH) catalyzes the second step in the physiologically important beta-oxidation pathway of fatty acid metabolism. This enzyme facilitates the syn-addition of a water molecule across the double bond of a trans-2-enoyl-CoA thioester, resulting in the formation of a beta-hydroxyacyl-CoA thioester. The catalytic mechanism of this proficient enzyme has been studied in great depth through a combination of kinetic, spectroscopic, and structural techniques, and is proposed to occur via the formation of a single transition state. Sequence alignment and mutagenesis studies have implicated the key residues important for catalysis: Gly-141, Glu-144, and Glu-164 (rat liver ECH numbering). The two catalytic glutamic acid residues are believed to act in concert to activate a water molecule, while Gly-141 is proposed to be involved in substrate activation. Recently, two potent inhibitors of ECH have been reported in the literature, which result in the irreversible inactivation of the enzyme via covalent adduct formation. This review summarizes studies on the structure, mechanism, and inhibition of ECH.
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas, Austin 78712, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Agnihotri
authors.forename: Hung-wen
authors.initials: HW
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D004746:Enoyl-CoA Hydratase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D014867:Water; D004746:Enoyl-CoA Hydratase