A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A
Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their relat...
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| Veröffentlicht in: | Evidence-based complementary and alternative medicine 2017-01, Vol.2017 (2017), p.1-8 |
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| creator | Lee, Jun-Ho Bae, Hyunsu Kim, Yoon Suh Eom, Sanung Jo, Heejin Yeom, Hye Duck Noh, Shinhwa Lee, Sung Bae Nam, Sangsoo |
| description | Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their related compounds. Coapplication with gomisin A inhibited the capsaicin-mediated inward peak current. This inhibitory effect of gomisin A on capsaicin-induced inward current showed concentration-dependence and was reversible. The half maximal inhibitory concentration of gomisin A was 62.7±8.4 µM. In addition, this inhibition occurred in a noncompetition regulation mode and voltage insensitive manner. Furthermore, molecular docking studies of gomisin A on TRPV1 showed that it interacted predominantly with residues at cavities in the segments 1 and 2 of each subunit. Four potential binding sites for this ligand in the extracellular region at sensor domain of TRPV1 channel were identified. Point mutagenesis studies were undertaken, and gomisin A potency decreased for both the Y453A and N467A mutants. The double mutation of Y453 and N467 significantly attenuated inhibitory effects by gomisin A. In summary, this study revealed the molecular basis for the interaction between TRPV1 and gomisin A and provides a novel potent interaction ligand. |
| doi_str_mv | 10.1155/2017/6451905 |
| format | Article |
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T.</contributor><creatorcontrib>Lee, Jun-Ho ; Bae, Hyunsu ; Kim, Yoon Suh ; Eom, Sanung ; Jo, Heejin ; Yeom, Hye Duck ; Noh, Shinhwa ; Lee, Sung Bae ; Nam, Sangsoo ; Carvalho, José C. T.</creatorcontrib><description>Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their related compounds. Coapplication with gomisin A inhibited the capsaicin-mediated inward peak current. This inhibitory effect of gomisin A on capsaicin-induced inward current showed concentration-dependence and was reversible. The half maximal inhibitory concentration of gomisin A was 62.7±8.4 µM. In addition, this inhibition occurred in a noncompetition regulation mode and voltage insensitive manner. Furthermore, molecular docking studies of gomisin A on TRPV1 showed that it interacted predominantly with residues at cavities in the segments 1 and 2 of each subunit. Four potential binding sites for this ligand in the extracellular region at sensor domain of TRPV1 channel were identified. Point mutagenesis studies were undertaken, and gomisin A potency decreased for both the Y453A and N467A mutants. The double mutation of Y453 and N467 significantly attenuated inhibitory effects by gomisin A. In summary, this study revealed the molecular basis for the interaction between TRPV1 and gomisin A and provides a novel potent interaction ligand.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2017/6451905</identifier><identifier>PMID: 29234417</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Bioactive compounds ; Capsaicin ; Capsaicin receptors ; Data analysis ; Deoxyribonucleic acid ; DNA ; Experiments ; Folk medicine ; Herbal medicine ; Immune system ; Inhibition ; Ligands ; Medical research ; Medicine ; Molecular biology ; Mutagenesis ; Mutants ; Proteins ; Regulation ; Schisandra ; Sensory neurons ; Transient receptor potential proteins ; Xenopus laevis</subject><ispartof>Evidence-based complementary and alternative medicine, 2017-01, Vol.2017 (2017), p.1-8</ispartof><rights>Copyright © 2017 Sung Bae Lee et al.</rights><rights>COPYRIGHT 2017 John Wiley & Sons, Inc.</rights><rights>Copyright © 2017 Sung Bae Lee et al.; This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2017 Sung Bae Lee et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-67ef9cebf58cee33c5d7e46ea2e942a576c5fb514320a0db36c6bb39acba32da3</citedby><cites>FETCH-LOGICAL-c525t-67ef9cebf58cee33c5d7e46ea2e942a576c5fb514320a0db36c6bb39acba32da3</cites><orcidid>0000-0002-0299-3582 ; 0000-0003-0913-8578</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684552/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684552/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29234417$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Carvalho, José C. T.</contributor><creatorcontrib>Lee, Jun-Ho</creatorcontrib><creatorcontrib>Bae, Hyunsu</creatorcontrib><creatorcontrib>Kim, Yoon Suh</creatorcontrib><creatorcontrib>Eom, Sanung</creatorcontrib><creatorcontrib>Jo, Heejin</creatorcontrib><creatorcontrib>Yeom, Hye Duck</creatorcontrib><creatorcontrib>Noh, Shinhwa</creatorcontrib><creatorcontrib>Lee, Sung Bae</creatorcontrib><creatorcontrib>Nam, Sangsoo</creatorcontrib><title>A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their related compounds. Coapplication with gomisin A inhibited the capsaicin-mediated inward peak current. This inhibitory effect of gomisin A on capsaicin-induced inward current showed concentration-dependence and was reversible. The half maximal inhibitory concentration of gomisin A was 62.7±8.4 µM. In addition, this inhibition occurred in a noncompetition regulation mode and voltage insensitive manner. Furthermore, molecular docking studies of gomisin A on TRPV1 showed that it interacted predominantly with residues at cavities in the segments 1 and 2 of each subunit. Four potential binding sites for this ligand in the extracellular region at sensor domain of TRPV1 channel were identified. Point mutagenesis studies were undertaken, and gomisin A potency decreased for both the Y453A and N467A mutants. The double mutation of Y453 and N467 significantly attenuated inhibitory effects by gomisin A. In summary, this study revealed the molecular basis for the interaction between TRPV1 and gomisin A and provides a novel potent interaction ligand.</description><subject>Bioactive compounds</subject><subject>Capsaicin</subject><subject>Capsaicin receptors</subject><subject>Data analysis</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Experiments</subject><subject>Folk medicine</subject><subject>Herbal medicine</subject><subject>Immune system</subject><subject>Inhibition</subject><subject>Ligands</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Molecular biology</subject><subject>Mutagenesis</subject><subject>Mutants</subject><subject>Proteins</subject><subject>Regulation</subject><subject>Schisandra</subject><subject>Sensory neurons</subject><subject>Transient receptor potential proteins</subject><subject>Xenopus laevis</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkU2LFDEQhhtR3A-9eZaAF2EdN9_pviyMi64LK4qM4i0k6eqdLJlkTLqV-fdmmHFcPXlKQj08qaq3aZ4R_JoQIc4pJupcckE6LB40x0RxMuO0bR8e7urbUXNSyh3GtFNKPW6OaEcZ50QdN3aOPqQAbgomozem-IKGlNG4BHQdl9760aeI0oAW2cTiIY7oMzhYjxX6lMb69iagryb6EJLv0WKzBkSQ3aCrtPLFRzR_0jwaTCjwdH-eNl_evV1cvp_dfLy6vpzfzJygYpxJBUPnwA6idQCMOdEr4BIMhY5TI5R0YrCCcEaxwb1l0klrWWecNYz2hp02FzvverIr6F3tLZug19mvTN7oZLz-uxL9Ut-mH1rIlgtBq-DlXpDT9wnKqOsEDkIwEdJUNOmU5JxJ2lb0xT_oXZpyrONVSpK6W3qfujUBtI9Dqv-6rVTPhZC42hSu1Ksd5XIqJcNwaJlgvY1YbyPW-4gr_vz-mAf4d6YVONsBSx9789P_pw4qA4P5QxNRVy3YL4qKt7A</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Lee, Jun-Ho</creator><creator>Bae, Hyunsu</creator><creator>Kim, Yoon Suh</creator><creator>Eom, Sanung</creator><creator>Jo, Heejin</creator><creator>Yeom, Hye Duck</creator><creator>Noh, Shinhwa</creator><creator>Lee, Sung Bae</creator><creator>Nam, Sangsoo</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0299-3582</orcidid><orcidid>https://orcid.org/0000-0003-0913-8578</orcidid></search><sort><creationdate>20170101</creationdate><title>A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A</title><author>Lee, Jun-Ho ; 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T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><addtitle>Evid Based Complement Alternat Med</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>2017</volume><issue>2017</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their related compounds. Coapplication with gomisin A inhibited the capsaicin-mediated inward peak current. This inhibitory effect of gomisin A on capsaicin-induced inward current showed concentration-dependence and was reversible. The half maximal inhibitory concentration of gomisin A was 62.7±8.4 µM. In addition, this inhibition occurred in a noncompetition regulation mode and voltage insensitive manner. Furthermore, molecular docking studies of gomisin A on TRPV1 showed that it interacted predominantly with residues at cavities in the segments 1 and 2 of each subunit. Four potential binding sites for this ligand in the extracellular region at sensor domain of TRPV1 channel were identified. Point mutagenesis studies were undertaken, and gomisin A potency decreased for both the Y453A and N467A mutants. The double mutation of Y453 and N467 significantly attenuated inhibitory effects by gomisin A. In summary, this study revealed the molecular basis for the interaction between TRPV1 and gomisin A and provides a novel potent interaction ligand.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>29234417</pmid><doi>10.1155/2017/6451905</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-0299-3582</orcidid><orcidid>https://orcid.org/0000-0003-0913-8578</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bioactive compounds Capsaicin Capsaicin receptors Data analysis Deoxyribonucleic acid DNA Experiments Folk medicine Herbal medicine Immune system Inhibition Ligands Medical research Medicine Molecular biology Mutagenesis Mutants Proteins Regulation Schisandra Sensory neurons Transient receptor potential proteins Xenopus laevis |
| title | A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A |
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