Homology modeling of GLUT4, an insulin regulated facilitated glucose transporter and docking studies with ATP and its inhibitors.
GLUT4 is a 12 transmembrane (TM) protein belonging to the Class I facilitated glucose transporter family that transports glucose into the cells in an insulin regulated manner. GLUT4 plays a key role in the maintenance of blood glucose homeostasis and inhibition of glucose transporter activity may lead to insulin resistance, hallmark of type 2 diabetes. No crystal structure data is available for any members of the facilitated glucose transporter family. Here, in this paper, we have generated a homology model of GLUT4 based on experimental data available on GLUT1, a Class I facilitated glucose transporter and the crystal structure data obtained from the Glycerol 3-phosphate transporter. The model identified regions in GLUT4 that form a channel for the transport of glucose along with the substrate interacting residues. Docking and electrostatic potential data analysis of GLUT4 model has mapped an ATP binding region close to the binding site of cytochalasin B and genistein, two GLUT4 inhibitors, and this may explain the mechanism by which these inhibitors could potentially affect the GLUT4 function.
Mohan S
Suma
S
School of Biotechnology, Amrita University, Kollam, Kerala 690525, India.
Perry
J Jefferson P
JJ
Poulose
Ninu
N
Nair
Bipin G
BG
Anilkumar
Gopalakrishnapillai
G
D000255:Adenosine Triphosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003571:Cytochalasin B / Q000737:chemistry*; D019833:Genistein / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry; D051272:Glucose Transporter Type 1 / Q000737:chemistry; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
C488962:GlpT protein, E coli; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D026901:Membrane Transport Proteins; C495692:SLC2A4 protein, human; D003571:Cytochalasin B; D000255:Adenosine Triphosphate; D019833:Genistein; D005947:Glucose