Glucokinase in the complex with glucose

The crystal structure of glucokinase in the complex with glucose reveals a palm shape. The polypeptide chain is composed of 448 amino acid residues that are distinctly folded into two domains of unequal size; the large and small domains. These are separated by a deep cleft, which forms the active site for phosphorylation, and an α anomer of the glucose molecule was observed to be bound to this active site in GK. The glucose binding site is located in the interdomain cleft and is composed of residues of the large domain (Glu256 and Glu290), the small domain (Thr168 and Lys169), and connecting region II (Asn204 and Asp205, shown in blue).

Shown here is the schematic drawing of domain composition and secondary structure of GK (1-11) in complex with glucose and compound A. Glucokinase is composed of the large domain (blue) and the small domain (cyan and magenta). Connecting regions I–III (green) connect the two domains. The C-terminal region of glucokinase forms the 13 helix (magenta) and is included in the small domain of GK(1-11). The glucose binding site (red circle) and an allosteric site (yellow oval) are positioned between two domains. 

Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y.

Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure 2004 (PubMed)

1V4T (PDB)

 Glucokinase in the complex with glucokinase regulatory protein (GKRP)

The interaction between GCK and GKRP reveals a large buried surface area, characterized by a limited number of polar and coulombic contacts. Glucokinase is shown in yellow, glucokinase regulatory protein - in red. All the rest of the presentation will be focused on the glucokinase-GKRP complex

Beck T, Miller BG.

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

4LC9 (PDB)

 

 

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