title: Constant pH molecular dynamics (CpHMD) and mutation studies: insights into AaegOBP1 pH-induced ligand releasing mechanism.
abstract: AaegOBP1, isolated from the male and female antenna of yellow fever mosquitoes, may serve as crucial molecular targets for the development of mosquitoes' attractants and for the control of mosquito populations. Nowadays crystal structures of AaegOBP1 in the neutral environment have been obtained, whereas little research is focused on the conformational change of AaegOBP1 in the acid solution. In our study, the conformational change and the ligand bound poses in different solution pH were investigated using constant pH molecular dynamics (CpHMD) as well as mutation studies. Results demonstrate that the protein changes dramatically in low pH solution and that the pH-sensing triad (Arg23-Tyr54-Ile125) plays an indispensable role in the structural stability and ligand binding. In addition, we have proved that the residue Arg23 is the most important one of the pH-sensing triad. This work could provide more penetrating understanding of the pH-induced ligand-releasing mechanism.
authors.affiliation: Jilin University, Changchun, People's Republic of China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Chu
authors.forename: Yun-Jian
authors.initials: YJ
authors.lastname: Wu
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhang
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xue
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
mesh_terms: D000143:Acids; D000330:Aedes / Q000737:chemistry*; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D057506:Arthropod Antennae / Q000737:chemistry*; D005260:Female; D006863:Hydrogen-Ion Concentration; D019476:Insect Proteins / Q000737:chemistry*; D007532:Isoleucine / Q000737:chemistry; D008024:Ligands; D008297:Male; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011487:Protein Conformation; D018035:Receptors, Odorant / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000143:Acids; D019476:Insect Proteins; D008024:Ligands; D018035:Receptors, Odorant; C045648:odorant-binding protein; D007532:Isoleucine; D014443:Tyrosine; D001120:Arginine