title: Molecular dynamics simulations of acylpeptide hydrolase bound to chlorpyrifosmethyl oxon and dichlorvos.
abstract: Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well as the different OP compounds binding and inducing conformational changes in two domains, namely, α/β hydrolase and β-propeller, remain poorly understood. We report a computational study of APH bound to chlorpyrifosmethyl oxon and dichlorvos. In our docking study, Val471 and Gly368 are important residues for chlorpyrifosmethyl oxon and dichlorvos binding. Molecular dynamics simulations were also performed to explore the conformational changes between the chlorpyrifosmethyl oxon and dichlorvos bound to APH, which indicated that the structural feature of chlorpyrifosmethyl oxon binding in APH permitted partial opening of the β-propeller fold and allowed the chlorpyrifosmethyl oxon to easily enter the catalytic site. These results may facilitate the design of APH-targeting drugs with improved efficacy.
authors: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130023, China. hyjin13@mails.jlu.edu.cn.
authors: Hanyong
authors: H
authors: Jin
authors: Second Bethune Hospital of Jilin University, Changchun 130041, China. zhouzhenhuan1979@163.com.
authors: Zhenhuan
authors: Z
authors: Zhou
authors: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130023, China. dmwang12@mails.jlu.edu.cn.
authors: Dongmei
authors: D
authors: Wang
authors: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China. guanss12@mails.jlu.edu.cn.
authors: Shanshan
authors: S
authors: Guan
authors: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130023, China. weiweihan@jlu.edu.cn.
authors: Weiwei
authors: W
authors: Han
mesh_terms: D004390:Chlorpyrifos / Q000737:chemistry* / Q000378:metabolism*; D004006:Dichlorvos / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D004006:Dichlorvos; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase; D004390:Chlorpyrifos