title: Interchain hydrogen-bonding interactions may facilitate translocation of K+ ions across the potassium channel selectivity filter, as suggested by synthetic modeling chemistry.
abstract: A 4-fold symmetric arrangement of TVGYG polypeptides forms the selectivity filter of the K+ channel from Streptomyces lividans (KcsA). We report the synthesis and properties of synthetic models for the filter, p-tert-butyl-calix[4]arene-(OCH(2)CO-XOBz)(4) (X = V, VG, VGY), 1-3. The first cation (Na+, K+) binds to the four -[OCH(2)CO]- units, a region devised to mimic the metal-binding site formed by the four T residues in KcsA. NMR studies reveal that cations and valine amide protons compete for the carbonyl oxygen atoms, converting NH(Val)...O=C hydrogen bonds to M+ ...O=C bonds (M+ = Na+ or K+). The strength of these interchain NH(Val)...O=C hydrogen bonds varies in the order 3 > 2 > 1. We propose that such interchain H-bonding may destabilize metal binding in the selectivity filter and thus help create the low energy barrier needed for rapid cation translocation.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Mareque Rivas
authors.forename: H
authors.initials: H
authors.lastname: Schwalbe
authors.forename: S J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D047250:Calixarenes; D002412:Cations / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D017136:Ion Transport; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D011188:Potassium / Q000737:chemistry / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013302:Streptomyces / Q000737:chemistry; D013698:Templates, Genetic; D014633:Valine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: C434726:4-tert-butylcalix(4)arene tetravaline benzyl ester; C434727:4-tert-butylcalix(4)arene tetravaline-glycine benzyl ester; C434728:4-tert-butylcalix(4)arene-tetravaline-glycine-tyrosine benzyl ester; D001426:Bacterial Proteins; D001952:Bridged-Ring Compounds; D002412:Cations; D004151:Dipeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D047250:Calixarenes; D014633:Valine; D011188:Potassium