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GSK-GKRP Interactions


A hydrophobic cleft on the GCK large domain (colored blue) consisting of Leu47, Leu58, Pro59, Tyr61, Met238, Leu243, and Val244 interacts with GKRP loop residues Pro462-Phe465 (colored yellow).

Hydrogen bonds
enhance interactions between the two proteins.
The hydrophobic interactions of GCK and GKRP contacts are reinforced by a hydrogen bond between Lys143 from the GCK small domain (white) and the backbone carbonyl group of Leu464 (black). Hydrogen bond is displayed as a yellow line connecting these two atoms.


The importance of 462–470 loop.
Repositioning of the GKRP 462–470 loop between the fructose 1-phosphate structure and the fructose 6- phosphate structure. Formation of the mammalian GCK-GKRP complex is stimulated by fructose 6-phosphate and antagonized by fructose 1-phosphate.

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Beck T, Miller BG

Structural Basis for Regulation of Human Glucokinase by Glucokinase Regulatory Protein. Biochemistry 2013 (PubMed)

4LC9(PDB)