Agnihotri Gautam, Liu Hung-wen
Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas, Austin 78712, USA.
Bioorg Med Chem. 2003 Jan 2;11(1):9-20. doi: 10.1016/s0968-0896(02)00333-4.
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.
烯酰辅酶A水合酶（ECH）催化脂肪酸代谢中生理上重要的β-氧化途径的第二步。该酶促进水分子跨反式-2-烯酰辅酶A硫酯的双键顺式加成，从而形成β-羟基酰基辅酶A硫酯。通过动力学、光谱学和结构技术的结合，对这种高效酶的催化机制进行了深入研究，并提出其通过形成单一过渡态来发生。序列比对和诱变研究已经确定了对催化重要的关键残基：Gly-141、Glu-144和Glu-164（大鼠肝脏ECH编号）。据信，两个催化性谷氨酸残基协同作用以激活一个水分子，而Gly-141被认为参与底物激活。最近，文献中报道了两种ECH的强效抑制剂，它们通过共价加合物的形成导致该酶不可逆失活。本综述总结了关于ECH的结构、机制和抑制作用的研究。
