Homology modeling of MT1 and MT2 receptors

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…The amine moiety interacts with Asn175 of TM4 in the MT 2 receptor; however, a corresponding amino acid in the MT1 receptor TM3 is not an Asn; rather, serines (Ser110 and Ser114) seem to bind to melatonin (see Fig. 5; Farce et al, 2008).…”

“…Taken together, the identification of sequence specific motifs may ultimately provide the molecular basis for the rational design of type specific therapeutic compounds. Farce et al (2008) have published models showing the predicted binding site for melatonin on the MT 1 and MT 2 melatonin receptors based on site-directed mutagenesis analysis and a three-dimensional homology modeling of the receptors using bovine rhodopsin as a template (Fig. 5).…”

“…The position in the transmembrane domain is indicated using the numbering scheme of Ballesteros and Weinstein (1995 Mazna et al, 2008 HEK, human embryonic kidney; CHO, Chinese hamster ovary. a Amino acid residues important for modulating binding to the MT 1 receptor (Farce et al, 2008). MELATONIN RECEPTORS ligand binding.…”

Homology Models of Melatonin Receptors: Challenges and Recent Advances

“…A further attempt to model the activated state of the MT 1 receptor was made by Farce et al in 2008 [63] based on the high resolution crystal structure of rhodopsin (PDB ID: 1L9H [61]). Interestingly, two gaps could be identified in the proposed alignment between rhodopsin and the MT 1 receptor sequences, located in TM6 and TM7.…”

“…Farce et al investigated the activation mechanism of MT 1 and MT 2 receptor subtypes [63]. As previously described for their MT 1 model, the authors inserted gaps in the alignment of rhodopsin and melatonin receptor TM sequences to improve the alignment quality.…”