Constant pH Molecular Dynamics (CpHMD) and mutation studies: Insights into AaegOBP1 pH-induced ligand releasing mechanism

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, wh...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2012-07, Vol.1824 (7), p.913-918
Main Authors: Chu, Wen-Ting, Wu, Yun-Jian, Zhang, Ji-Long, Zheng, Qing-Chuan, Chen, Lin, Xue, Qiao, Zhang, Hong-Xing
Format: Article
Language:English
Subjects:
AaegOBP1
Acids
Aedes - chemistry
Animals
Arginine - chemistry
Arthropod Antennae - chemistry
attractants
CpHMD
crystal structure
Culicidae
Female
females
Hydrogen-Ion Concentration
Insect Proteins - chemistry
Isoleucine - chemistry
Ligands
Male
males
molecular dynamics
Molecular Dynamics Simulation
mosquito control
Mutation
Odorant binding protein
pH dependent
pH-induced ligand releasing
Protein Conformation
Receptors, Odorant - chemistry
Tyrosine - chemistry
Yellow fever virus
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Summary: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. [Display omitted] ► we perform CpHMD simulations to explain the conformational change from pH 7 to 5. ► pKa prediction of AaegOBP1 is calculated after MD simulation.
ISSN:1570-9639
0006-3002
1878-1454
DOI:10.1016/j.bbapap.2012.03.008