| http://purl.uniprot.org/citations/24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24523403 | http://www.w3.org/2000/01/rdf-schema#comment | "P-glycoprotein (P-gp, ABCB1) is an ATP-binding cassette drug pump that protects us from toxic compounds and confers multidrug resistance. Each homologous half contains a transmembrane domain with six transmembrane segments followed by a nucleotide-binding domain (NBD). The drug- and ATP-binding sites reside at the interface between the transmembrane domain and NBDs, respectively. Drug binding activates ATPase activity by an unknown mechanism. There is no high resolution structure of human P-gp, but homology models based on the crystal structures of bacterial, mouse, and Caenorhabditis elegans ATP-binding cassette drug pumps yield both open (NBDs apart) and closed (NBDs together) conformations. Molecular dynamics simulations predict that the NBDs can be separated over a range of distances (over 20 Å). To determine the distance that show high or low ATPase activity, we cross-linked reporter cysteines L175C (N-half) and N820C (C-half) with cross-linkers of various lengths that separated the halves between 6 and 30 Å (α-carbons). We observed that ATPase activity increased over 10-fold when the cysteines were cross-linked at distances between 6 and 19 Å, although cross-linking at distances greater than 20 Å yielded basal levels of activity. The results suggest that the ATPase activation switch appears to be turned on or off when L175C/N820 are clamped at distances less than or greater than 20 Å, respectively. We predict that the high/low ATPase activity switch may occur at a distance where the NBDs are predicted in molecular dynamic simulations to undergo pronounced twisting as they approach each other (Wise, J. G. (2012) Biochemistry 51, 5125-5141)."xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m114.552075"xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/author | "Clarke D.M."xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/author | "Loo T.W."xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/pages | "8484-8492"xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/title | "Identification of the distance between the homologous halves of P-glycoprotein that triggers the high/low ATPase activity switch."xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://purl.uniprot.org/core/volume | "289"xsd:string |
| http://purl.uniprot.org/citations/24523403 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24523403 |
| http://purl.uniprot.org/citations/24523403 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24523403 |
| http://purl.uniprot.org/uniprot/#_F4ZUY5-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_A1L471-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_A4D1D2-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_A8E2S6-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_B5U2G4-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_F4ZUQ5-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_F4ZUT2-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_F4ZUV0-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_F4ZUV4-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_F4ZUX9-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_O60213-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_P08183-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |
| http://purl.uniprot.org/uniprot/#_Q6TBL4-mappedCitation-24523403 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24523403 |