| pubmed-article:20394729 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C0242643 | lld:lifeskim |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C0205177 | lld:lifeskim |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C0026377 | lld:lifeskim |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C0175721 | lld:lifeskim |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C2825407 | lld:lifeskim |
| pubmed-article:20394729 | lifeskim:mentions | umls-concept:C0587267 | lld:lifeskim |
| pubmed-article:20394729 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:20394729 | pubmed:dateCreated | 2010-5-10 | lld:pubmed |
| pubmed-article:20394729 | pubmed:abstractText | The P-glycoprotein (P-gp, ABCB1) drug pump protects us from toxic compounds and confers multidrug resistance. Each of the two homologous halves of P-gp is composed of a transmembrane domain (TMD) with six TM segments followed by a nucleotide-binding domain (NBD). The drug- and ATP-binding sites reside at the interface between the TMDs and NBDs, respectively. Crystal structures show drug pumps in the open and closed conformations, where the drug-binding pocket and NBDs are open or closed at the cytoplasmic side, respectively. Although it has been postulated that drug substrates enter the drug-binding pocket in the open conformation, it is unknown if they can enter in the closed conformation. To determine this, we introduced cysteines into regions of TM3 (residues 175-178) and TM9 (residues 820-822) that extend into the cytoplasm and are 4 A and 20 A apart in the closed and open conformations, respectively. The 12 double cysteine mutants were then cross-linked with a short cross-linker, M1M (4 A) at 0 degrees C to reduce thermal motion in the protein. Only mutant L175C/N820C was cross-linked. Cross-linking was not increased in the presence of ATP or drug substrates. Cross-linking increased its basal ATPase activity about 3-fold. Activity could be increased further by drug substrates such as verapamil and rhodamine B. These results suggest that P-gp in the membrane is in the closed conformation that has a high affinity for drug substrates. | lld:pubmed |
| pubmed-article:20394729 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20394729 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20394729 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20394729 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20394729 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20394729 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20394729 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20394729 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20394729 | pubmed:month | May | lld:pubmed |
| pubmed-article:20394729 | pubmed:issn | 1090-2104 | lld:pubmed |
| pubmed-article:20394729 | pubmed:author | pubmed-author:LooTip WTW | lld:pubmed |
| pubmed-article:20394729 | pubmed:author | pubmed-author:ClarkeDavid... | lld:pubmed |
| pubmed-article:20394729 | pubmed:author | pubmed-author:BartlettM... | lld:pubmed |
| pubmed-article:20394729 | pubmed:copyrightInfo | Copyright (c) 2010 Elsevier Inc. All rights reserved. | lld:pubmed |
| pubmed-article:20394729 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20394729 | pubmed:day | 7 | lld:pubmed |
| pubmed-article:20394729 | pubmed:volume | 395 | lld:pubmed |
| pubmed-article:20394729 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20394729 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20394729 | pubmed:pagination | 436-40 | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:meshHeading | pubmed-meshheading:20394729... | lld:pubmed |
| pubmed-article:20394729 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20394729 | pubmed:articleTitle | Human P-glycoprotein is active when the two halves are clamped together in the closed conformation. | lld:pubmed |
| pubmed-article:20394729 | pubmed:affiliation | Department of Medicine, University of Toronto, Toronto, Ontario, Canada. | lld:pubmed |
| pubmed-article:20394729 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20394729 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:5243 | entrezgene:pubmed | pubmed-article:20394729 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:20394729 | lld:entrezgene |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:20394729 | lld:pubmed |
