Homology modelling of the serotoninergic 5-HT2c receptor.
Since its discovery, 5-hydroxytryptamine, more usually called serotonin, has been an elusive candidate as a major mood regulator. This capacity gives it a great importance in the treatment of depression. It is within this framework that our work takes place, as it is related more particularly to a new therapeutic class whose leader is agomelatine. This compound binds to the melatoninergic receptors and to the serotoninergic 5-HT2c receptor, giving rise to the MASSA concept (Melatonin Agonist and Selective Serotonin Antagonist). Like the majority of the serotoninergic receptors, the sub-type 5-HT2c is a G-protein coupled receptor (GPCR). The three-dimensional structure of 5-HT2c is not experimentally known, and we thus resorted to comparative homology modelling to build a model allowing us to study its interactions with agomelatine.
Farce
Amaury
A
Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Thérapeutique, EA 1043, 3 rue du professeur Laguesse, BP 83, 59006 Lille Cedex, France.
Dilly
Sebastien
S
Yous
Said
S
Berthelot
Pascal
P
Chavatte
Philippe
P
D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D008090:Lisuride / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013386:Succinates / Q000737:chemistry* / Q000494:pharmacology; D009281:Naphthalenes
D000081:Acetamides; D008090:Lisuride; D044405:Receptor, Serotonin, 5-HT2C; D012243:Rhodopsin; D013386:Succinates; C084711:agomelatine; D009281:Naphthalenes; C064294:sarpogrelate