Upon insulin stimulation, GLUT4 is quickly transported from these intracellular structures to the plasma membrane, resulting in rapid consumption of glucose from blood 9. The major facilitator superfamily (MFS) glucose transporter GLUT4 mediates the rate-limiting glucose cellular uptake in adipocytes and muscle cells, and thus plays a vital role in insulin-responsive glucose metabolism 3, 4, 5, 6.Īt basal state, GLUT4 is primarily distributed on the membranes of the trans-Golgi network (TGN), endosomes and 50–70 nm tubulo-vesicular structures known as the GLUT4 storage vesicles (GSVs) 7, 8.
Insulin lowers blood sugar level by triggering cellular uptake of glucose 2. Our results provide a better understanding of the molecular role of the M2 site in GI substrate recognition.ĭivision of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea Institute of Life Science and Natural Resources, Korea University, Seoul, Republic of Korea.Glucose, being the primary fuel, a versatile bio-precursor, and a signaling molecule, is tightly controlled for metabolic homeostasis via various mechanisms, such as hormonal regulation by insulin and glucagon 1. We suggest a two-step sequential process for SruGI substrate recognition, in Mn 2+ binding mode, at the M2 site. The metal binding geometry of the M2 site indicates a distorted octahedral coordination with an angle of 55-110°, whereas the M1 site has a relatively stable octahedral coordination with an angle of 85-95°. Glucose and Mn 2+ at the M2 site were bridged by water molecules using a hydrogen bonding network. Glucose molecule can only bind to the M1 site in presence of Mn 2+ at the M2 site. Metal binding at the M2 site elicits a configuration change at the M1 site. This study provides a snapshot of metal binding at the SruGI M2 site in the presence of Mn 2+, but not in the presence of Mg 2+. Here, we report the crystal structure of the two metal binding modes of SruGI and its complex with glucose. Although we assessed inhibitor binding at the M1 site, the metal binding at the M2 site and the substrate recognition mechanism for SruGI remains the unclear. We recently determined the crystal structure of GI from S. rubiginosus (SruGI) complexed with a xylitol inhibitor in one metal binding mode. This is one of the most important enzymes in the production of high-fructose corn syrup (HFCS) and biofuel. Glucose isomerase (GI) catalyzes the reversible enzymatic isomerization of d-glucose and d-xylose to d-fructose and d-xylulose, respectively. Diversity, Equity, Inclusion, and Access.
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