Glucokinase Regulatory Protein

spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Glucokinase (Hexokinase 4) Regulatory Protein Glucokinase regulatory protein is also known as glucokinase (hexokinase 4) regulator. This protein is important in the metabolism of glucose in the body. It maintains the location and activity of the enzyme glucokinase (hexokinase 4). Regulation occurs through competitive inhibition of glucokinase. The regulating protein binds to glucokinase, thus inhibiting glucokinase's activity. The regulatory protein is not present in the liver, where it's substrate is bio-synthesized. Conversely, the regulatory protein is present in liver cells where glucokinase is synthesized. Disease GCKR variants affect the glucose and lipid homeostasis and are associated with hypertriglyceridaemia. Mutations in glucokinase regulatory protein can contribute to type 2 diabetes and hyperinsulinemic hypoglycemia. Both of these health issues involve either high or low levels of blood glucose. Glucokinase Regulatory Protein Structure This protein is made up of 626 amino acids, and it weighs 68 kDa. This protein is trilobal, with two identical sugar isomerase (SIS) domains (SIS-1 is in red and SIS-2 is in blue), and one alpha-helical c-terminal lid domain. The sugar isomerase domains are dominated by 5 stranded parallel beta-sheets that are flanked on either side by alpha-helices, Effectively making an alpha-beta-alpha motif. The lid domain consists of seven alpha-helices, with a triple helical core. The core is flanked by a single helix that runs parallel to the triple helix. The remaining helices run perpendicular to the triple helix. There are 14 residues that act as links between the domains. Regulation Mechanism In the presence of fructose 6-phosphate, glucokinase regulatory protein is activated and releases the enzyme glucokinase. Fructose 6-phosphate is produced when glucose is present in concentrations higher than will be immediately digested. The regulatory protein is also antagonized by fructose 1-phosphate. In essence, the regulatory protein is activated when glucose is ready to be stored, and inactivated when the storage process is complete. Gluokinase regulatory protein controls the location of glucokinase, which is important in the digestion of glucose. The enzyme phosphorylates glucose, in preparation for storage in the form of glycogen.

3D structures of glucokinase regulatory protein

Updated on 31-March-2019

4bb9 – hGKRP (mutant) + fructose-1-phosphate – human
4bba – hGKRP (mutant) + phosphate
4ly9 – hGKRP + sorbitol-6-phosphate + piperazine derivative
4mqu, 4mro – hGKRP + piperazine derivative + glucitol derivative
4msu, 4ohk, 4ohm, 4oho, 4ohp, 4olh – hGKRP + piperazine derivative + sorbitol-6-phosphate
4op1, 4op2, 4op3, 4pxs – hGKRP + pyridine derivative + sorbitol-6-phosphate
4px2, 4px3, 4px5 – hGKRP + sulfonamide derivative + sorbitol-6-phosphate
3w0l – GKRP + glucokinase – Xenopus laevis
4lc9 – GKRP + glucokinase – rat

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