http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#Head http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://www.nanopub.org/nschema#hasAssertion http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#assertion http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://www.nanopub.org/nschema#hasProvenance http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#provenance http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://www.nanopub.org/nschema#hasPublicationInfo http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#pubinfo http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#assertion http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_1 http://purl.obolibrary.org/obo/RO_0002204 http://www.informatics.jax.org/marker/MGI:88388 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_36080 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_2 http://www.selventa.com/vocabulary/translocationFrom http://amigo.geneontology.org/amigo/term/GO:0005622 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_2 http://www.selventa.com/vocabulary/translocationOf http://resource.belframework.org/belframework/1.0/namespace/selventa-legacy-chemical-names/Chloride%281-%29 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_2 http://www.selventa.com/vocabulary/translocationTo http://amigo.geneontology.org/amigo/term/GO:0005576 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_3 http://purl.obolibrary.org/obo/BFO_0000066 http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=10090 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_3 http://www.w3.org/1999/02/22-rdf-syntax-ns#object http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_2 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_3 http://www.w3.org/1999/02/22-rdf-syntax-ns#predicate http://www.selventa.com/vocabulary/increases http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_3 http://www.w3.org/1999/02/22-rdf-syntax-ns#subject http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_1 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_3 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.w3.org/1999/02/22-rdf-syntax-ns#Statement http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#assertion http://www.w3.org/2000/01/rdf-schema#label p(MGI:Cftr) -> sec(a(SCHEM:"Chloride(1-)")) http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#provenance http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 61,000 statements. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_4 http://www.w3.org/ns/prov#value The cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts Cl- current. We explored the CFTR pore by studying voltage-dependent blockade of the channel by two organic anions: glibenclamide and isethionate. To simplify the kinetic analysis, a CFTR mutant, K1250A-CFTR, was used because this mutant channel, once opened, can remain open for minutes. Dose-response relationships of both blockers follow a simple Michaelis-Menten function with K(d) values that differ by three orders of magnitude. Glibenclamide blocks CFTR from the intracellular side of the membrane with slow kinetics. Both the on and off rates of glibenclamide block are voltage dependent. Removing external Cl- increases affinity of glibenclamide due to a decrease of the off rate and an increase of the on rate, suggesting the presence of a Cl- binding site external to the glibenclamide binding site. Isethionate blocks the channel from the cytoplasmic side with fast kinetics, but has no measurable effect when applied extracellularly. Increasing the internal Cl- concentration reduces isethionate block without affecting its voltage dependence, suggesting that Cl- and isethionate compete for a binding site in the pore. The voltage dependence and external Cl- concentration dependence of isethionate block are nearly identical to those of glibenclamide block, suggesting that these two blockers may bind to a common binding site, an idea further supported by kinetic studies of blocking with glibenclamide/isethionate mixtures. By comparing the physical and chemical natures of these two blockers, we propose that CFTR channel has an asymmetric pore with a wide internal entrance and a deeply embedded blocker binding site where local charges as well as hydrophobic components determine the affinity of the blockers. http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12407077 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12407077 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#_4 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g#pubinfo http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://purl.org/dc/terms/created 2014-07-03T14:30:06.846+02:00 http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAvJXSHjdJNLZ8Zhfnswo5lzmhO18m_TsUh4tGIis-G-g http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234