1dgk
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of | + | Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of two structurally similar halves connected by an alpha-helix. The enzyme dimerizes at elevated protein concentrations in solution and in crystal structures; however, almost all published data reflect the properties of a hexokinase I monomer in solution. Crystal structures of mutant forms of recombinant human hexokinase I, presented here, reveal the enzyme monomer for the first time. The mutant hexokinases bind both glucose 6-phosphate and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide chain. Exposure of the monomer crystals to ADP in the complete absence of glucose 6-phosphate reveals a second binding site for adenine nucleotides at the putative active site (C-half), with conformational changes extending 15 A to the contact interface between the N and C-halves. The structures reveal distinct conformational states for the C-half and a rigid-body rotation of the N-half, as possible elements of a structure-based mechanism for allosteric regulation of catalysis. |
==Disease== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: The Glycolytic Enzymes]] | [[Category: The Glycolytic Enzymes]] | ||
| - | [[Category: Aleshin, A | + | [[Category: Aleshin, A E.]] |
| - | [[Category: Bartunik, H | + | [[Category: Bartunik, H D.]] |
| - | [[Category: Bourenkov, G | + | [[Category: Bourenkov, G P.]] |
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
[[Category: Kirby, C.]] | [[Category: Kirby, C.]] | ||
[[Category: Liu, X.]] | [[Category: Liu, X.]] | ||
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[[Category: sugar kinase]] | [[Category: sugar kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:29 2008'' |
Revision as of 10:16, 21 February 2008
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MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I WITH GLUCOSE AND ADP IN THE ACTIVE SITE
Contents |
Overview
Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of two structurally similar halves connected by an alpha-helix. The enzyme dimerizes at elevated protein concentrations in solution and in crystal structures; however, almost all published data reflect the properties of a hexokinase I monomer in solution. Crystal structures of mutant forms of recombinant human hexokinase I, presented here, reveal the enzyme monomer for the first time. The mutant hexokinases bind both glucose 6-phosphate and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide chain. Exposure of the monomer crystals to ADP in the complete absence of glucose 6-phosphate reveals a second binding site for adenine nucleotides at the putative active site (C-half), with conformational changes extending 15 A to the contact interface between the N and C-halves. The structures reveal distinct conformational states for the C-half and a rigid-body rotation of the N-half, as possible elements of a structure-based mechanism for allosteric regulation of catalysis.
Disease
Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[142600]
About this Structure
1DGK is a Single protein structure of sequence from Homo sapiens with , and as ligands. The following page contains interesting information on the relation of 1DGK with [The Glycolytic Enzymes]. Active as Hexokinase, with EC number 2.7.1.1 Full crystallographic information is available from OCA.
Reference
Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation., Aleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB, J Mol Biol. 2000 Mar 3;296(4):1001-15. PMID:10686099
Page seeded by OCA on Thu Feb 21 12:16:29 2008
