title: Binding modes of phosphotriesterase-like lactonase complexed with δ-nonanoic lactone and paraoxon using molecular dynamics simulations.
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.
authors.affiliation: a National Engineering Laboratory For AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences , Jilin University , Changchun 130012 , China.|b State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Guan
authors.affiliation: a National Engineering Laboratory For AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences , Jilin University , Changchun 130012 , China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: a National Engineering Laboratory For AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences , Jilin University , Changchun 130012 , China.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Jin
authors.affiliation: c Editorial Department of Journal of Jilin University (Science Edition) , Changchun , China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shan
authors.affiliation: a National Engineering Laboratory For AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences , Jilin University , Changchun 130012 , China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Han
authors.affiliation: b State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: a National Engineering Laboratory For AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences , Jilin University , Changchun 130012 , China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Shan
mesh_terms: D001665:Binding Sites; D006860:Hydrogen Bonding; D007783:Lactones / Q000737:chemistry*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010261:Paraoxon / Q000737:chemistry*; D044345:Phosphoric Triester Hydrolases / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding
chemical_list: D007783:Lactones; D008024:Ligands; D044345:Phosphoric Triester Hydrolases; D010261:Paraoxon
keywords: docking; free energy calculations; molecular dynamics; phosphotriesterase-like lactonase