Presence of carbohydrate binding modules in extracellular region of class C G-protein coupled receptors (C GPCR): An in silico investigation on sweet taste receptor
Sweet taste receptor (STR) is a C GPCR family member and a suggested drug target for metabolic disorders such asdiabetes. Detailed characteristics of the molecule as well as its ligand interactions mode are yet considerably unclear due toexperimental study limitations of transmembrane proteins. An in silico study was designed to find the putative carbohydratebinding sites on STR. To this end, a-D-glucose and its a-1,4-oligomers (degree of polymerization up to 14) were chosen asprobes and docked into an ensemble of different conformations of the extracellular region of STR monomers (T1R2 andT1R3), using AutoDock Vina. Ensembles had been sampled from an MD simulation experiment. Best poses were furtherenergy-minimized in the presence of water molecules with Amber14 forcefield. For each monomer, four distinct bindingregions consisting of one or two binding pockets could be distinguished. These regions were further investigated withregard to hydrophobicity and hydrophilicity of the residues, as well as residue compositions and non-covalent interactionswith ligands. Popular binding regions showed similar characteristics to carbohydrate binding modules (CBM). Observationof several conserved or semi-conserved residues in these binding regions suggests a possibility to extrapolate the results toother C GPCR family members. In conclusion, presence of CBM in STR and, by extrapolation, in other C GPCR familymembers is suggested, similar to previously proposed sites in gut fungal C GPCRs, through transcriptome analyses. STRmodes of interaction with carbohydrates are also discussed and characteristics of non-covalent interactions in C GPCRfamily are highlighted.
Volume 45, 2020
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