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Journal of Biosciences

, 44:138 | Cite as

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

  • Elaheh Kashani-Amin
  • Amirhossein Sakhteman
  • Bagher Larijani
  • Azadeh Ebrahim-HabibiEmail author
Article
  • 59 Downloads

Abstract

Sweet taste receptor (STR) is a C GPCR family member and a suggested drug target for metabolic disorders such as diabetes. Detailed characteristics of the molecule as well as its ligand interactions mode are yet considerably unclear due to experimental study limitations of transmembrane proteins. An in silico study was designed to find the putative carbohydrate binding sites on STR. To this end, α-D-glucose and its α-1,4-oligomers (degree of polymerization up to 14) were chosen as probes and docked into an ensemble of different conformations of the extracellular region of STR monomers (T1R2 and T1R3), using AutoDock Vina. Ensembles had been sampled from an MD simulation experiment. Best poses were further energy-minimized in the presence of water molecules with Amber14 forcefield. For each monomer, four distinct binding regions consisting of one or two binding pockets could be distinguished. These regions were further investigated with regard to hydrophobicity and hydrophilicity of the residues, as well as residue compositions and non-covalent interactions with ligands. Popular binding regions showed similar characteristics to carbohydrate binding modules (CBM). Observation of several conserved or semi-conserved residues in these binding regions suggests a possibility to extrapolate the results to other C GPCR family members. In conclusion, presence of CBM in STR and, by extrapolation, in other C GPCR family members is suggested, similar to previously proposed sites in gut fungal C GPCRs, through transcriptome analyses. STR modes of interaction with carbohydrates are also discussed and characteristics of non-covalent interactions in C GPCR family are highlighted.

Keywords

α-D-glucose carbohydrate binding modules CBM oligomer sweet taste receptor 

Nomenclature and abbreviations used

3Glc to 14Glc: Ligands

Αlpha-D-glucose will be called glucose, disaccharide composed of two 1,4-α-D-glucoses units maltose and oligomers of 3 to 14 units of glucose will be called 3Glc to 14Glc.

To clarify characteristics of atomic interactions of oligomers, each pyranose unit is numbered as follows

the first α-D-glucose with its C1 binded to C4 of the next glucose unit is numbered as 1 and others are numbered serially; for example, 3Glc-2 means the second gluco-pyranose unit of the tri-saccharide ligand.

Other nomenclature adopted by YASARA (software used for docking, please see details in Methods section)

Atoms of each molecule are shown as the name of the molecule or residue followed by the name of the atom; for example, 3Glc-2-O3 means atom O3 of 3Glc-2 and GLY 502-O means oxygen atom of G502.

Core residues

residues in common between binding pockets located in each distinct region

EC

extracellular part of STR

H-Bond

hydrogen bond

HP-interaction

hydrophobic interaction

MDS

molecular dynamic simulations

STR

sweet taste receptor

TMD

trans-membrane domain

Notes

Acknowledgements

This study was performed as a Ph.D. thesis granted by Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Supplementary material

12038_2019_9944_MOESM1_ESM.docx (6.2 mb)
Supplementary material 1 (DOCX 6377 kb)

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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  2. 2.Department of Medicinal Chemistry, School of PharmacyShiraz University of Medical SciencesShirazIran
  3. 3.Medicinal Chemistry and Natural Products Research CenterShiraz University of Medical SciencesShirazIran
  4. 4.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran

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