1v4t
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1v4t |SIZE=350|CAPTION= <scene name='initialview01'>1v4t</scene>, resolution 3.40Å | |PDB= 1v4t |SIZE=350|CAPTION= <scene name='initialview01'>1v4t</scene>, resolution 3.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1v4t|1V4T]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1v4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v4t OCA], [http://www.ebi.ac.uk/pdbsum/1v4t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1v4t RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138079 138079]], Diabetes mellitus, noninsulin-dependent, late onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138079 138079]], Diabetes mellitus, permanent neonatal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138079 138079]], Hyperinsulinemic hypoglycemia, familial, 3 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138079 138079]], MODY, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138079 138079]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 31: | Line 31: | ||
[[Category: Nagata, Y.]] | [[Category: Nagata, Y.]] | ||
[[Category: Nishimura, T.]] | [[Category: Nishimura, T.]] | ||
| - | [[Category: NA]] | ||
| - | [[Category: SO4]] | ||
[[Category: allosteric enzyme]] | [[Category: allosteric enzyme]] | ||
[[Category: diabetes]] | [[Category: diabetes]] | ||
[[Category: hexokinase iv]] | [[Category: hexokinase iv]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:19:27 2008'' |
Revision as of 21:19, 30 March 2008
| |||||||
| , resolution 3.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Hexokinase, with EC number 2.7.1.1 | ||||||
| Related: | 1V4T
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human glucokinase
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.
About this Structure
1V4T is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Mon Mar 31 00:19:27 2008
