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|3qic, resolution 2.20Å ()|
|Gene:||GCK (Homo sapiens)|
|Related:|| 1v4s, 3id8, 3f9m
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.
Crystal structure of E339K mutated human glucokinase reveals changes in the ATP binding site., Liu Q, Shen Y, Liu S, Weng J, Liu J, FEBS Lett. 2011 Apr 20;585(8):1175-9. Epub 2011 Mar 22. PMID:21420961
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.