4NO7

Human Glucokinase in complex with a nanomolar activator.

Summary for 4NO7

• Entry DOI: 10.2210/pdb4no7/pdb
• Related: 1V4S 3ID8
• Descriptor: Glucokinase, alpha-D-glucopyranose, (2R)-2-[3-chloro-4-(methylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]-N-(pyrazin-2-yl)propanamide, ... (4 entities in total)
• Functional Keywords: kinase, pancreas, transferase-transferase activator complex, transferase/transferase activator
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 53598.24

Authors

Petit, P.,Ferry, G.,Antoine, M.,Boutin, J.A.,Kotschy, A.,Perron-Sierra, F.,Mamelli, L.,Vuillard, L. (deposition date: 2013-11-19, release date: 2014-10-29, Last modification date: 2023-09-20)

Primary citation

Petit, P.,Antoine, M.,Ferry, G.,Boutin, J.A.,Lagarde, A.,Gluais, L.,Vincentelli, R.,Vuillard, L.
The active conformation of human glucokinase is not altered by allosteric activators.
Acta Crystallogr. D Biol. Crystallogr., 67:929-935, 2011

PubMed Abstract: Glucokinase (GK) catalyses the formation of glucose 6-phosphate from glucose and ATP. A specific feature of GK amongst hexokinases is that it can cycle between active and inactive conformations as a function of glucose concentration, resulting in a unique positive kinetic cooperativity with glucose, which turns GK into a unique key sensor of glucose metabolism, notably in the pancreas. GK is a target of antidiabetic drugs aimed at the activation of GK activity, leading to insulin secretion. Here, the first structures of a GK-glucose complex without activator, of GK-glucose-AMP-PNP and of GK-glucose-AMP-PNP with a bound activator are reported. All these structures are extremely similar, thus demonstrating that binding of GK activators does not result in conformational changes of the active protein but in stabilization of the active form of GK.

PubMed: 22101819
DOI: 10.1107/S0907444911036729

Experimental method

X-RAY DIFFRACTION (1.7 Å)