| Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies. | |
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MedLine Citation:
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PMID: 21448716 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1-TM6). TRPV1 is found in the central and peripheral nervous system, and it is an important therapeutic target for pain relief. We describe here the construction of a tetrameric homology model of rat TRPV1 (rTRPV1). We experimentally evaluated by mutational analysis the contribution of residues of rTRPV1 contributing to ligand binding by the prototypical TRPV1 agonists, capsaicin and resiniferatoxin (RTX). We then performed docking analysis using our homology model. The docking results with capsaicin and RTX showed that our homology model was reliable, affording good agreement with our mutation data. Additionally, the binding mode of a simplified RTX (sRTX) ligand as predicted by the modeling agreed well with those of capsaicin and RTX, accounting for the high binding affinity of the sRTX ligand for TRPV1. Through the homology modeling, docking and mutational studies, we obtained important insights into the ligand-receptor interactions at the molecular level which should prove of value in the design of novel TRPV1 ligands. |
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Authors:
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Jin Hee Lee; Yoonji Lee; HyungChul Ryu; Dong Wook Kang; Jeewoo Lee; Jozsef Lazar; Larry V Pearce; Vladimir A Pavlyukovets; Peter M Blumberg; Sun Choi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2011-03-30 |
Journal Detail:
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Title: Journal of computer-aided molecular design Volume: 25 ISSN: 1573-4951 ISO Abbreviation: J. Comput. Aided Mol. Des. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-05-13 Completed Date: 2011-08-26 Revised Date: 2012-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8710425 Medline TA: J Comput Aided Mol Des Country: Netherlands |
Other Details:
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Languages: eng Pagination: 317-27 Citation Subset: IM |
Affiliation:
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College of Pharmacy, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Analgesics / chemistry*, pharmacology Animals CHO Cells Capsaicin / chemistry*, pharmacology Cricetinae Cricetulus DNA Mutational Analysis Diterpenes / chemistry*, pharmacology Ligands Models, Molecular* Molecular Sequence Data Mutation Pain Management Protein Conformation Rats TRPV Cation Channels / agonists*, chemistry*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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Z01 BC005270-27/BC/NCI NIH HHS; ZIA BC005270-28/BC/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Analgesics; 0/Diterpenes; 0/Ligands; 0/TRPV Cation Channels; 0/Trpv1 protein, rat; 404-86-4/Capsaicin; 57444-62-9/resiniferatoxin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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