title: Quantitative structure-activity relationship analysis of the cation permeability of the P2X2 channel.
abstract: The membrane-embedded, ligand-gated P2X glycoprotein receptor is a monovalent-bivalent cation channel that is activated by physiological concentrations of extracellular ATP. A quantitative structure-activity relationship (QSAR) analysis was developed to model the cation permeability of the P2X2 channel and its mutants. As chemical properties, the helix-coil equilibrium constants and the distribution coefficients of the system octanol/water at pH 7.4 were applied and modified (sliding windows) according to Eroshkin et al. (Comput. Appl. Biosci., 1995, 11, 49-44). The results were visualized by a dimeric P2X2 channel construct. The results support the hypothesis that residues which put into the cavity and contribute to hydrogen bonding forces are involved to a control of the transport of hydrated cations through the P2X2 channel. The model may be useful to develop P2X2 receptor antagonists.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Leipzig, Saxony, Germany. magp@medizin.uni-leipzig.de
authors.forename: Peter P
authors.initials: PP
authors.lastname: Mager
authors.forename: Anje
authors.initials: A
authors.lastname: Weber
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
mesh_terms: D000818:Animals; D002412:Cations / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010539:Permeability; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058476:Receptors, Purinergic P2X2; D013329:Structure-Activity Relationship
chemical_list: D002412:Cations; D007473:Ion Channels; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2