1v4t

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Revision as of 17:35, 12 November 2007

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spinqualitylabelsall models 1v4t, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of human glucokinase

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Glucokinase is a monomeric enzyme that displays a low affinity for glucose, and a sigmoidal saturation curve for its substrate, two properties that, are important for its playing the role of a glucose sensor in pancreas and, liver. The molecular basis for these two properties is not well, understood. Herein we report the crystal structures of glucokinase in its, active and inactive forms, which demonstrate that global conformational, change, including domain reorganization, is induced by glucose binding., This suggests that the positive cooperativity of monomeric glucokinase, obeys the "mnemonical mechanism" rather than the well-known concerted, model. These structures also revealed an allosteric site through which, small molecules may modulate the kinetic properties of the enzyme. This, finding provided the mechanistic basis for activation of glucokinase as a, potential therapeutic approach for treating type 2 diabetes mellitus.

Disease

Known diseases associated with this structure: Diabetes mellitus, gestational OMIM:[138079], Diabetes mellitus, noninsulin-dependent, late onset OMIM:[138079], Diabetes mellitus, permanent neonatal OMIM:[138079], Hyperinsulinemic hypoglycemia, familial, 3 OMIM:[138079], MODY, type II OMIM:[138079]

About this Structure

1V4T is a Single protein structure of sequence from Homo sapiens with SO4 and NA as ligands. Active as Hexokinase, with EC number 2.7.1.1 Full crystallographic information is available from OCA.

Reference

Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase., Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y, Structure. 2004 Mar;12(3):429-38. PMID:15016359

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