Open and closed states of Mrlip1 DAG lipase revealed by molecular dynamics simulation. Issue 18 (12th December 2018)

• Record Type: Journal Article
• Authors: Ali, Shahid; Khan, Faez Iqbal; Chen, Wenwen; Rahaman, Abdul; Wang, Yonghua
• Is Part Of: Molecular simulation. Volume 44:Issue 18(2018)
• Page Start: 1520
• Page End: 1528
• Publication Date: 2018-12-12
• Subjects: Lipase -- catalytic triad -- gating mechanism -- computational modelling -- mutation analysis; Molecular dynamics -- Computer simulation -- Periodicals; Statistical mechanics -- Computer simulation -- Periodicals; 539.6
• DOI: 10.1080/08927022.2018.1513647
• Languages: English
• ISSNs: 0892-7022

Abstract

ABSTRACT: The lid and flap domains control the catalytic activity of lipase through the opening and closing motion. However, this gating mechanism of diacylglycerol (DAG) lipase is poorly understood due to the lack of 3D structures in open conformations. In this study, the opening and closing states of Mrlip1 DAG lipase are revealed by the homology modelling and molecular dynamic simulations. It was found that the active residues (Ser171, His281 and Asp228 ) in the catalytic pocket of Mrlip1 DAG lipase are covered by the lid domain in the closed conformation, and exposed to the solvent in the open conformation. The role of residues Phe278 and Gln282 in the flap domain, as well as that of Thr101 and Thr107 in the lid domains are also identified in gating mechanism. The site-directed mutagenesis have been carried out to illustrate the putative alterations of enzyme specificity. Our results suggest that the substrate specificity is achieved by these two key residues Phe278 and Gln282, and the irreversible conversion from DAG to TAG (Triacylglycerol) lipase are enabled by the two-point mutations.