| A pharmacological organization of G protein-coupled receptors. | |
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MedLine Citation:
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PMID: 23291723 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Protein classification typically uses structural, sequence or functional similarity. Here we introduce an orthogonal method that organizes proteins by ligand similarity, focusing on the class A G-protein-coupled receptor (GPCR) protein family. Comparing a ligand-based dendrogram to a sequence-based one, we identified GPCRs that were distantly linked by sequence but were neighbors by ligand similarity. Experimental testing of the ligands predicted to link three of these new pairs confirmed the predicted association, with potencies ranging from low nanomolar to low micromolar. We also predicted hundreds of non-GPCRs closely related to GPCRs by ligand similarity and confirmed several cases experimentally. Ligand similarities among these targets may reflect the conservation of identical ligands among unrelated receptors, which signal in different time domains. Our method integrates these apparently disparate receptors into chemically coherent circuits and suggests which of these receptors may be targeted by individual ligands. |
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Authors:
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Henry Lin; Maria F Sassano; Bryan L Roth; Brian K Shoichet |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2013-01-06 |
Journal Detail:
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Title: Nature methods Volume: 10 ISSN: 1548-7105 ISO Abbreviation: Nat. Methods Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-30 Completed Date: 2013-03-28 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101215604 Medline TA: Nat Methods Country: United States |
Other Details:
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Languages: eng Pagination: 140-6 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Binding Sites Databases, Protein Humans Ligands* Receptors, G-Protein-Coupled / chemistry*, classification*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DA017204/DA/NIDA NIH HHS; GM71896/GM/NIGMS NIH HHS; R01 GM071896/GM/NIGMS NIH HHS; R01 MH61887/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Receptors, G-Protein-Coupled |
| Comments/Corrections | |
Comment In:
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Nat Rev Drug Discov. 2013 Mar;12(3):187
[PMID:
23411721
]
Nat Methods. 2013 Feb;10(2):116-7 [PMID: 23361090 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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