3QIC

The structure of human glucokinase E339K mutation

Summary for 3QIC

• Entry DOI: 10.2210/pdb3qic/pdb
• Related: 1V4S 3F9M 3ID8
• Descriptor: Glucokinase, alpha-D-glucopyranose, GLYCEROL, ... (4 entities in total)
• Functional Keywords: glycolysis, kinase, sugar binding, phosphorylation, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 53808.95

Authors

Liu, Q.,Liu, S.,Liu, J. (deposition date: 2011-01-27, release date: 2011-06-01, Last modification date: 2024-10-30)

Primary citation

Liu, Q.,Shen, Y.,Liu, S.,Weng, J.,Liu, J.
Crystal structure of E339K mutated human glucokinase reveals changes in the ATP binding site.
Febs Lett., 585:1175-1179, 2011

PubMed Abstract: 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.

PubMed: 21420961
DOI: 10.1016/j.febslet.2011.03.026

Experimental method

X-RAY DIFFRACTION (2.2 Å)