title: Prediction of 5-HT3 receptor agonist-binding residues using homology modeling.
abstract: 5-HT(3) receptors demonstrate significant structural and functional homology to other members of the Cys-loop ligand-gated ion channel superfamily. The extracellular domains of these receptors share similar sequence homology (approximately 20%) with Limnaea acetylcholine binding protein, for which an x-ray crystal structure is available. We used this structure as a template for computer-based homology modeling of the 5-HT(3) receptor extracellular domain. AutoDock software was used to dock 5-HT into the putative 5-HT(3) receptor ligand-binding site, resulting in seven alternative energetically favorable models. Residues located no more than 5 A from the docked 5-HT were identified for each model; of these, 12 were found to be common to all seven models with five others present in only certain models. Some docking models reflected the cation-pi interaction previously demonstrated for W183, and data from these and other studies were used to define our preferred models.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1AG, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Reeves
authors.forename: Muhammed F R
authors.initials: MF
authors.lastname: Sayed
authors.forename: Pak-Lee
authors.initials: PL
authors.lastname: Chau
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Price
authors.forename: Sarah C R
authors.initials: SC
authors.lastname: Lummis
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003198:Computer Simulation; D045604:Extracellular Fluid / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017385:Sequence Homology; D017366:Serotonin Receptor Agonists / Q000737:chemistry
chemical_list: C428944:AChBP protein, Lymnaea; D002352:Carrier Proteins; D021122:Protein Subunits; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists