Infections by mosquito-borne diseases represent one of the leading causes of death in third world countries.The rapid progression of resistance to conventional insecticide causes a significant threat to the highly eff...Infections by mosquito-borne diseases represent one of the leading causes of death in third world countries.The rapid progression of resistance to conventional insecticide causes a significant threat to the highly efficient preventive methods currently in place.Insect neuropeptidergic system offers potential targets to control the insect vectors.The essential roles of the neuropeptide ecdysis triggering hormone(ETH)in insect development and reproduction led us to attempt understanding of the fundamentals of the biochemical interaction between ETH and its receptor in the African malaria mosquito Anopheles gambiae.One of two ETH peptides of the African malaria mosquito(AgETH1),a small peptide hormone with 17 amino acid residues(SESPGFFIKLSKSVPRI-NH2),was studied to elucidate its molecular structure.N-termini deletions and mutations of conserved amino acids in the ligand revealed the critical residues for the receptor activation.The solution structure of AgETH1 using 2D 1H-1H nuclear magnetic resonance(NMR)spectroscopy and nuclear overhauser effect(NOE)derived constraints revealed a short alpha helix between residues 3S and 11S.The NMR solution structure of AgETH1 will be of significant assistance for designing a new class of insecticidal compounds that acts on the AgETH receptor aiming for in silico docking studies.展开更多
基金supported by National Institutes of Health(NIH)grants NIH-NIAID R21 AI135457 and AI163423,1S10OD026726 and USDA-NIFA,GRANT13066347thank the Terry Johnson Cancer Research Center of Kansas State University and K-INBRE(NIH Grant P20GM103418)programs for supporting NMR studies.Contribution number 22-200-J from the Kansas Agricultural Experiment Station.
文摘Infections by mosquito-borne diseases represent one of the leading causes of death in third world countries.The rapid progression of resistance to conventional insecticide causes a significant threat to the highly efficient preventive methods currently in place.Insect neuropeptidergic system offers potential targets to control the insect vectors.The essential roles of the neuropeptide ecdysis triggering hormone(ETH)in insect development and reproduction led us to attempt understanding of the fundamentals of the biochemical interaction between ETH and its receptor in the African malaria mosquito Anopheles gambiae.One of two ETH peptides of the African malaria mosquito(AgETH1),a small peptide hormone with 17 amino acid residues(SESPGFFIKLSKSVPRI-NH2),was studied to elucidate its molecular structure.N-termini deletions and mutations of conserved amino acids in the ligand revealed the critical residues for the receptor activation.The solution structure of AgETH1 using 2D 1H-1H nuclear magnetic resonance(NMR)spectroscopy and nuclear overhauser effect(NOE)derived constraints revealed a short alpha helix between residues 3S and 11S.The NMR solution structure of AgETH1 will be of significant assistance for designing a new class of insecticidal compounds that acts on the AgETH receptor aiming for in silico docking studies.
