1cza
From Proteopedia
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MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE, GLUCOSE-6-PHOSPHATE, AND ADP
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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
1CZA is a Single protein structure of sequence from Homo sapiens with GLC, G6P and ADP as ligands. 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 Mon Nov 12 16:26:55 2007
