The Anopheles gambiae is a highly anthropophilic mosquito which is the leading vector for malaria. This disease has affected more than 500 million people worldwide. The Anopheles gambiae targets its hosts through the odors of the human skin and sweat where odorant molecules radiate. These odors elicit specific responses from the insect through the odorant – binding proteins (OBP). Recently, a specific type of OBP has been characterized which is known as the Anopheles gambiae odorant – binding protein 20 (AgamOBP20). This OBP is highly expressed in the female mosquito antennae during the peak of its host – seeking behavior and thus may play a role in olfactory perception. The binding site of the AgamOBP20 is composed primarily of hydrophobic residues wherein the importance of each residue is herein analysed to further understand the properties of AgamOBP20. This was carried out through computer – aided site – directed mutagenesis coupled with homology modelling and docking simulations wherein each residue in the binding site was changed to alanine and serine. Probable key amino acid residues were identified as LEU106, LEU107, and MET53 which are hypothesized to play a significant role in the protein – ligand interaction. These residues had the greatest impact in the binding free energy when mutated with alanine and serine. The presented results suggest that steric hindrance and hydrophobic interaction are crucial factors to consider on the manner in which the ligand binds with AgamOBP20. The molecular features and parameters obtained may be utilized for the development of new pesticides and repellents that are able to block the function of AgamOBP20 and may result to the disarray of the host – seeking behavior of the Anopheles gambiae.
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ARNOLD K. BORDOLI L. KOPP J. SCHWEDE T.: The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics 22(2) 2005 195-201.
BERMAN H.M. WESTBROOK J. FENG Z. GILLILAND G. BHAT T.N. WEISSIG H. BOURNE P.E.: The Protein Databank. Nuc. Acids Res. 28(1) 2000 235-242.
BIASINI M. BIENERT S. WATERHOUSE A. ARNOLD K. STUDER G. SCHMIDT T. SCHWEDE T.: SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information. Nuc. Acids Res. 42(1) 2014 252-258.
BIESSMANN H. NGUYEN Q.K. LE D. WALTER M.F.: Microarray-based survey of a subset of putative olfactory genes in the mosquito Anopheles gambiae. Insect Mol. Biol. 14 2005 575-589.
BORDOLI L. KIEFER F. ARNOLD K. BENKERT P. BATTEY J. SCHWEDE T.: Protein structure homology modelling using SWISS-MODEL Workspace. Nat. Protoc. 4 2009 1-13.
HLAVACEK W.S. POSNER R.G. PERELSON A.S.: Steric effects on multivalent ligand-receptor binding: exclusion of ligand sites by bound cell surface receptors. Biophys. J. 76(6) 1999 3031-3043.
JANAIRO J.I.B. JANAIRO G.C.: Homology modeling and comparative docking analysis of two naturally occurring pancreatic glucokinase mutants. Philipp. Sci. Lett. 5(1) 2012 1-6.
JANAIRO J.I.B. CARANDANG J. VI AMALIN D.: Docking simulations and regression analysis on the binding of several carboxylic acids with the odorant - binding protein 20 of Anopheles gambiae. Rom. J. Biochem. 52(1) 2015 61-65.
KNOLS B.G.J. VAN LOON J.J.A. CORK A. ROBINSON R.D. ADAM W. MEIJERINK J. DE JONG R. TAKKEN W.: Behavioural and electrophysiological responses of the female malaria mosquito Anopheles gambiae (Diptera: Culicidae) to Limburger cheese volatiles Bull. Entomol. Res. 87 1997 151-159.
ODA A. TAKAHASHI O.: Validation of ArgusLab efficiencies for binding free energy calculations. Chem. Bio. Informat. J. 9 2009 52-61.
PELOSI P. MAIDA R.: Odorant binding proteins in vertebrates and insects: similarities and possible common function. Chem. Senses. 15 1990 205-215.
PELOSI P. TIRINDELLI R.: Structure/activity studies and characterization of an odorant-binding protein. Receptor events and transduction in taste and olfaction. Chem. Senses 1 1989 207-226.
PEVSNER J. REED R.R. FEINSTEIN P.G. SNYDER S.H.: Molecular cloning of odorant-binding protein: member of a ligand carrier family. Science 241 1988 336-339.
RUND S.S.C. HOU T.Y. WARD S.M. COLLINS F.H. DUFFIELD G.E.: Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae. Proc. Natl. Acad. Sci. USA 108 2001 E421-E430.
SCHWEDE T. KOPP J. GUEX N. PEITSCH M.C.: SWISS-MODEL: an automated protein homologymodeling server. Nuc. Acids Res. 31(13) 2003 3381-3385.
SNYDER P.W. MECINOVIC J. MOUSTAKAS D.T. THOMAS S.W. HARDER M. MACK E.T. LOCKETT M.R. HÉROUX A. SHERMAN W. WHITESIDES G.M.: Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase. Proc. Natl. Acad. Sci. USA 108(44) 2011 17889-17894.
ZIEMBA B.P. MURPHY E.J. EDLIN H.T. JONES D.N.M.: A novel mechanism of ligand binding and release in the odorant binding protein 20 from the malaria mosquito Anopheles gambiae Protein Sci. 22 2013 11-21.