Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Cong, Xiaojing | ko |
dc.contributor.author | Cheron, Jean-Baptiste | ko |
dc.contributor.author | Golebiowski, Jerome | ko |
dc.contributor.author | Antonczak, Serge | ko |
dc.contributor.author | Fiorucci, Sebastien | ko |
dc.date.accessioned | 2019-07-11T08:12:54Z | - |
dc.date.available | 2019-07-11T08:12:54Z | - |
dc.date.created | 2019-05-30 | - |
dc.date.issued | 2019-06 | - |
dc.identifier.citation | Journal of Chemical Information and Modeling, v.59, no.6, pp.2871 - 2878 | - |
dc.identifier.issn | 1549-9596 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/10121 | - |
dc.description.abstract | Positive allosteric modulators (PAMs) of metabotropic glutamate receptor type 5 (mGluR 5 ), a prototypical class C G protein-coupled receptor (GPCR), have shown therapeutic potential for various neurological disorders. Understanding the allosteric activation mechanism is essential for the rational design of mGluR 5 PAMs. We studied the actions of positive and negative allosteric modulators within the transmembrane domain of mGluR 5 , using enhance-sampling all-atom molecular dynamics simulations. We found dual binding modes of the PAM, associated with distinct shapes of the allosteric pocket. The negative allosteric modulators, in contrast, showed only one binding mode. The simulations revealed the mechanism by which the PAM activated the receptor, in the absence of the orthosteric agonist (the so-called allosteric agonism). The mechanism relied on dynamic communications between amino-acid motifs that are highly conserved across class C GPCRs. The findings may guide structure-based design and virtual screening of allosteric modulators for mGluR 5 as well as for other class C GPCRs. © 2019 American Chemical Society. | - |
dc.language | English | - |
dc.publisher | American Chemical Society | - |
dc.title | Allosteric Modulation Mechanism of the mGIuR(5) Transmembrane Domain | - |
dc.type | Article | - |
dc.identifier.doi | 10.1021/acs.jcim.9b00045 | - |
dc.identifier.wosid | 000473116500033 | - |
dc.identifier.scopusid | 2-s2.0-85065839478 | - |
dc.type.local | Article(Overseas) | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.contributor.nonIdAuthor | Cong, Xiaojing | - |
dc.contributor.nonIdAuthor | Cheron, Jean-Baptiste | - |
dc.contributor.nonIdAuthor | Antonczak, Serge | - |
dc.contributor.nonIdAuthor | Fiorucci, Sebastien | - |
dc.identifier.citationVolume | 59 | - |
dc.identifier.citationNumber | 6 | - |
dc.identifier.citationStartPage | 2871 | - |
dc.identifier.citationEndPage | 2878 | - |
dc.identifier.citationTitle | Journal of Chemical Information and Modeling | - |
dc.type.journalArticle | Article | - |
dc.description.isOpenAccess | N | - |
dc.subject.keywordPlus | METABOTROPIC GLUTAMATE RECEPTORS | - |
dc.subject.keywordPlus | CONFORMATIONAL SELECTION | - |
dc.subject.keywordPlus | HEPTAHELICAL DOMAIN | - |
dc.subject.keywordPlus | AGONIST INDUCTION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | ENSEMBLE | - |
dc.subject.keywordPlus | FAMILY | - |
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