单酰甘油脂肪酶
催化三位一体
水解酶
丝氨酸水解酶
内大麻素系统
脂肪酶
化学
丝氨酸
配体(生物化学)
生物化学
立体化学
活动站点
酶
受体
作者
Thomas Bertrand,Franck Augé,Jacques Houtmann,Alexey Rak,François Vallée,Vincent Mikol,Pierre‐François Berne,Nadine Michot,D. Cheuret,Chloé Hoornaert,Magali Mathieu
标识
DOI:10.1016/j.jmb.2009.11.060
摘要
Monoglyceride lipase (MGL) is a serine hydrolase that hydrolyses 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. 2-AG is an endogenous ligand of cannabinoid receptors, involved in various physiological processes in the brain. We present here the first crystal structure of human MGL in its apo form and in complex with the covalent inhibitor SAR629. MGL shares the classic fold of the alpha/beta hydrolase family but depicts an unusually large hydrophobic occluded tunnel with a highly flexible lid at its entry and the catalytic triad buried at its end. Structures reveal the configuration of the catalytic triad and the shape and nature of the binding site of 2-AG. The bound structure of SAR629 highlights the key interactions for productive binding with MGL. The shape of the tunnel suggests a high druggability of the protein and provides an attractive template for drug discovery.
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