Prediction of 5-HT3 receptor agonist-binding residues using homology modeling.
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.
Reeves
David C
DC
Department of Biochemistry, University of Cambridge, Cambridge CB2 1AG, United Kingdom.
Sayed
Muhammed F R
MF
Chau
Pak-Lee
PL
Price
Kerry L
KL
Lummis
Sarah C R
SC
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
C428944:AChBP protein, Lymnaea; D002352:Carrier Proteins; D021122:Protein Subunits; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists