| pubmed-article:10860944 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C0065898 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1523873 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1521991 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1167622 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1709915 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1880022 | lld:lifeskim |
| pubmed-article:10860944 | lifeskim:mentions | umls-concept:C1511545 | lld:lifeskim |
| pubmed-article:10860944 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:10860944 | pubmed:dateCreated | 2000-8-10 | lld:pubmed |
| pubmed-article:10860944 | pubmed:abstractText | A molecular model of the human melanin-concentrating hormone (MCH) peptide was constructed and docked into a helical, bacteriorhodopsin-based model of the recently identified human MCH receptor. From this hormone-receptor complex, potential sites of agonist-receptor interaction were identified, and site-directed mutagenesis was used to substitute residues predicted to reside within the receptor binding pocket. Substitution of Asp(123)(3.32) in the third transmembrane domain of the receptor resulted in a loss of detectable (125)I-MCH binding and of MCH-stimulated Ca(2+) flux; cell surface expression of the mutant receptor was not affected. Arg(11) and Arg(14) of the MCH ligand were identified as potential sites of interaction with Asp(123)(3.32). [Ala(14)]-MCH was equipotent to native MCH in its ability to bind to and activate the wild-type MCH receptor, whereas [Ala(11)]-MCH displayed a 3000-fold reduction in binding affinity and a complete loss of measurable functional activity. Furthermore, [Lys(11)]-MCH and [D-Arg(11)]-MCH displayed reduced affinity for the receptor. [Lys(11)]-MCH was observed to be a partial agonist, eliciting approximately 67% of the native peptide's activity in a Ca(2+) flux assay, and [D-Arg(11)]-MCH was determined to be a functional antagonist with a K(b) valve of 15.8 microM. These data provide evidence that a basic moiety with specific stereochemical requirements at this site is needed for receptor activation. We conclude that both Asp(123)(3.32) in the MCH receptor and Arg(11) in the MCH peptide are required for the formation of the MCH peptide/receptor complex and propose that they form a direct interaction that is critical for receptor function. | lld:pubmed |
| pubmed-article:10860944 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10860944 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10860944 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10860944 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:10860944 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10860944 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10860944 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:10860944 | pubmed:issn | 0026-895X | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:DurkinJ PJP | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:ZhangRR | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:StraderC DCD | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:YanYY | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:MurgoloNN | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:GrazianoM PMP | lld:pubmed |
| pubmed-article:10860944 | pubmed:author | pubmed-author:MacdonaldDD | lld:pubmed |
| pubmed-article:10860944 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10860944 | pubmed:volume | 58 | lld:pubmed |
| pubmed-article:10860944 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10860944 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10860944 | pubmed:pagination | 217-25 | lld:pubmed |
| pubmed-article:10860944 | pubmed:dateRevised | 2005-11-17 | lld:pubmed |
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| pubmed-article:10860944 | pubmed:meshHeading | pubmed-meshheading:10860944... | lld:pubmed |
| pubmed-article:10860944 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:10860944 | pubmed:articleTitle | Molecular characterization of the melanin-concentrating hormone/receptor complex: identification of critical residues involved in binding and activation. | lld:pubmed |
| pubmed-article:10860944 | pubmed:affiliation | Department of Central Nervous System and Cardiovascular Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. douglas.mcdonald@spcorp.com | lld:pubmed |
| pubmed-article:10860944 | pubmed:publicationType | Journal Article | lld:pubmed |
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