論文 - 詳細
RRC ID | 47635 |
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著者 | Ohbuchi K, Mori Y, Ogawa K, Warabi E, Yamamoto M, Hirokawa T. |
タイトル | Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study. |
ジャーナル | PLoS One |
Abstract |
Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity. The detailed binding mode of each ligand was then simulated by computational analysis. As a result, three amino acids (L518, F591 and L670) were newly identified as being involved in ligand binding and/or modulation of proton sensitivity. In addition, in silico docking simulation and a subsequent mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in a unique manner. These results provide novel insights into the binding mode of various vanilloids to the channel and will be helpful in developing a TRPV1 modulator. |
巻・号 | 11(9) |
ページ | e0162543 |
公開日 | 2016-1-1 |
DOI | 10.1371/journal.pone.0162543 |
PII | PONE-D-16-20075 |
PMID | 27606946 |
PMC | PMC5015962 |
MeSH | Amino Acids / chemistry Calcium / metabolism Capsaicin / chemistry Capsaicin / pharmacology Catechols / chemistry Catechols / pharmacology DNA Mutational Analysis Diterpenes / chemistry Diterpenes / pharmacology Fatty Alcohols / chemistry Fatty Alcohols / pharmacology Humans Kinetics Ligands Models, Molecular* Molecular Docking Simulation Mutant Proteins / chemistry Mutant Proteins / metabolism Mutation / genetics* Point Mutation / genetics Protons Reproducibility of Results Sequence Homology, Amino Acid Structure-Activity Relationship TRPV Cation Channels / agonists* TRPV Cation Channels / chemistry TRPV Cation Channels / genetics* |
IF | 2.74 |
引用数 | 9 |
WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
リソース情報 | |
遺伝子材料 | pcDNA3.1-hTRPV1-FLAG WT (RDB14587) pcDNA3.1-hTRPV1-FLAG-C158A (RDB14588) pcDNA3.1-hTRPV1-FLAG-L515A (RDB14589) pcDNA3.1-hTRPV1-FLAG-L518A (RDB14590) pcDNA3.1-hTRPV1-FLAG-L547A (RDB14591) pcDNA3.1-hTRPV1-FLAG-T550A (RDB14592) pcDNA3.1-hTRPV1-FLAG-I573A (RDB14593) pcDNA3.1-hTRPV1-FLAG-F587A (RDB14594) pcDNA3.1-hTRPV1-FLAG-F591A (RDB14595) pcDNA3.1-hTRPV1-FLAG-L670A (RDB14596) pcDNA3.1-hTRPV1-FLAG-S512A (RDB14597) pcDNA3.1-hTRPV1-FLAG-Y511F (RDB14598). |