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J Insect Physiol

Title:		Molecular modeling of the binding of pheromone biosynthesis activating neuropeptide to its receptor
Author(s):		Stern PS; Yu L; Choi MY; Jurenka RA; Becker L; Rafaeli A;
Address:		"Chemical Physics Department, Weizmann Institute of Science, 76100 Rehovot, Israel"
Journal Title:		J Insect Physiol
Year:		2007
Volume:		20070401
Issue:		8
Page Number:		803 - 818
DOI:		10.1016/j.jinsphys.2007.03.012
ISSN/ISBN:		0022-1910 (Print) 0022-1910 (Linking)
Abstract:		"Moth sex-pheromone biosynthesis follows a circadian cycle, which is cued by the release of the neurohormone pheromone biosynthesis activating neuropeptide (PBAN) to the hemolymph. PBAN binds to a G protein-coupled receptor (GPCR), in pheromone glands, (PG) initially identified by us in Helicoverpa zea moths (HezPBAN-R). In this study, the sequences of the seven transmembrane helices of HezPBAN-R were identified, built, packed and oriented correctly after multiple sequence alignment of the HezPBAN-R and several other GPCRs using the X-ray structure of rhodopsin as a template. Molecular dynamics simulations were run on three different beta-turn types of the C-terminal hexapeptide of PBAN and the results clustered into 12 structurally distinct groups. The lowest energy conformation from each group was used for computer-simulated docking with the model of the HezPBAN-R. Highest scoring complexes were examined and putative binding sites were identified. Experimental studies, using in vitro PG, revealed lower levels of pheromonotropic activity when challenged with pyrokinin-like peptides than with HezPBAN as ligand. Thus, the Drosophila melanogaster pyrokinin-1 receptor (CG9918) was chosen to create chimera receptors by exchanging between the three extracellular loops of the HezPBAN-R and the CG9918 for in silico mutagenesis experiments. The predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells"
Keywords:		"Amino Acid Sequence Animals Binding Sites Models, Molecular Molecular Sequence Data Moths/*metabolism Neuropeptides/chemistry/*metabolism Protein Structure, Tertiary;"
Notes:		"MedlineStern, Peter S Yu, Lian Choi, Man-Yeon Jurenka, Russell A Becker, Liron Rafaeli, Ada eng Research Support, Non-U.S. Gov't England 2007/05/22 J Insect Physiol. 2007 Aug; 53(8):803-18. doi: 10.1016/j.jinsphys.2007.03.012. Epub 2007 Apr 1"