3QIC: The structure of human glucokinase E339K mutation

Human glucokinase (GK) plays an important role in glucose homeostasis. An E339K mutation in GK was recently found to be associated with hyperglycemia. It showed lower enzyme activity and impaired protein stability compared to the wild-type enzyme. Here, we present the crystal structure of E339K GK in complex with glucose. This mutation results in a conformational change of His416, spatially interfering with adenosine-triphosphate (ATP) binding. Furthermore, Ser411 at the ATP binding site is phosphorylated and then hydrogen bonded with Thr82, physically blocking the ATP binding. These findings provide structural basis for the reduced activity of this mutant.
PDB ID: 3QICDownload
MMDB ID: 91000
PDB Deposition Date: 2011/1/27
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 3QIC: monomeric; determined by author and by software (PISA)
Molecular Components in 3QIC
Label Count Molecule
Protein (1 molecule)
Glucokinase(Gene symbol: GCK)
Molecule annotation
Chemicals (7 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB