Glycerol is Released from a New Path in MGL Lipase Catalytic Process

作者：Lan, Dongming; Li, Shu; Tang, Wei; Zhao, Zexin; Luo, Mupeng; Yuan, Shuguang^*; Xu, Jun; Wang, Yonghua^*

来源：Journal of Chemical Information and Modeling, 2022, 62(9): 2248-2256.

DOI：10.1021/acs.jcim.1c00708

• MONOACYLGLYCEROL LIPASE
• CONFORMATIONAL SELECTION
• INDUCED FIT
• MONOGLYCERIDE LIPASE
• BACTERIAL
• BINDING
• ENZYME
• DYNAMICS

Traditionally, it is believed that the substrate and products of a monoacylglycerol lipase (MGL) share the same path to enter and exit the catalytic site. Glycerol (a product of MGL), however, was recently hypothesized to be released through a different path. In order to improve the catalytic efficacy and thermo-stability of MGL, it is important to articulate the pathways of a MGL products releasing. In this study, with structure biological approaches, biochemical experiments, and in silico methods, we prove that glycerol is released from a different path in the catalytic site indeed. The fatty acid (another product of MGL) does share the same binding path with the substrate. This discovery paves a new road to design MGL inhibitors or optimize MGL catalytic efficacy.

• 单位
  中山大学; 中国科学院