Binding modes of phosphotriesterase-like lactonase complexed with δ-nonanoic lactone and paraoxon using molecular dynamics simulations. Issue 2 (25th January 2017)

• Record Type: Journal Article
• Authors: Guan, Shanshan; Zhao, Li; Jin, Hanyong; Shan, Ning; Han, Weiwei; Wang, Song; Shan, Yaming
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 35:Issue 2(2017)
• Page Start: 273
• Page End: 286
• Publication Date: 2017-01-25
• Subjects: phosphotriesterase-like lactonase -- docking -- molecular dynamics -- free energy calculations; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2016.1142899
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract : Phosphotriesterase-like lactonases (PLLs) have received much attention because of their physical and chemical properties. They may have widespread applications in various fields. For example, they show potential for quorum-sensing signaling pathways and organophosphorus (OP) detoxification in agricultural science. However, the mechanism by which PLLs hydrolyze, which involves OP compounds and lactones and a variety of distinct catalytic efficiencies, has only rarely been explored. In the present study, molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of DrPLL, a member of the PLL superfamily in Deinococcus radiodurans, bound to two substrates, δ -nonanoic lactone and paraoxon. It has been observed that there is a 16-fold increase in the catalytic efficiency of the two mutant strains of DrPLL (F26G/C72I) vs. the wild-type enzyme toward the hydrolysis of paraoxon, but an explanation for this behavior is currently lacking. The analysis of the molecular trajectories of DrPLL bound to δ -nonanoic lactone indicated that lactone-induced conformational changes take place in loop 8, which is near the active site. Binding to paraoxon may lead to conformational displacement of loop 1 residues, which could lead to the deformation of the active site and so trigger the entry of the paraoxon into the active site. The efficiency of the F26G/C72I mutant was increased by decreasing the displacement of loop 1 residues and increasing the flexibility of loop 8 residues. These results provide a molecular-level explanation for the experimental behavior.