title: Relative similarity within purine nucleotide and ligand structures operating on nitric oxide synthetase, guanylyl cyclase and potassium (K ATP, BK Ca) channels.
abstract: OBJECTIVE
  Purine nucleotides play a central role in signal transduction events initiated at the cell membrane. The NO-cGMP-cGK pathway, in particular, mediates events involving NOS and some classes of K(+) ion channel. The aim of this study is to investigate relative molecular similarity within the ligands binding to NOS, K(ATP), BK(Ca) channels and regulatory nucleotides.
  
  
  METHODS
  Minimum energy conformers of the ligand structures were superimposed and fitted to L-arginine and the nucleotides of adenine and guanine using a computational program.
  
  
  RESULTS
  Distinctive patterns were evident in the fitting of NOS isoform antagonists to L-arginine. K(ATP) channel openers and antagonists superimposed on the glycosidic linkage and imidazole ring of the purine nucleotides, and guanidinium and ribose groups of GTP in the case of glibenclamide. The fits of BK(Ca) channel openers and antagonists to cGMP were characterized by the linear dimensions of their structures; distances between terminal oxy groups in respect of dexamethasone and aldosterone.
  
  
  CONCLUSIONS
  The findings provide structural evidence for the functional interaction between K(+) channel openers/antagonists and the regulatory nucleotides. Use of the purine nucleotide template systematizes the considerable heterogeneity evident within the structures of ligands operating on K(+) ion channels.
authors.affiliation: Faculty of Health, Sport & Science, University of Glamorgan, Cardiff, UK. wrwillia@glam.ac.uk
authors.forename: W Robert
authors.initials: WR
authors.lastname: Williams
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000450:Aldosterone / Q000737:chemistry / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003907:Dexamethasone / Q000737:chemistry / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D019001:Nitric Oxide Synthase / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008024:Ligands; D026902:Potassium Channel Blockers; D000450:Aldosterone; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP