1DGK

MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I WITH GLUCOSE AND ADP IN THE ACTIVE SITE

Summary for 1DGK

• Entry DOI: 10.2210/pdb1dgk/pdb
• Related: 1CZA 1HKB 1HKC
• Descriptor: HEXOKINASE TYPE I, alpha-D-glucopyranose, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: brain hexokinase, mammalian hexokinase 1, sugar kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 103866.67

Authors

Aleshin, A.E.,Liu, X.,Kirby, C.,Bourenkov, G.P.,Bartunik, H.D.,Fromm, H.J.,Honzatko, R.B. (deposition date: 1999-11-24, release date: 2000-03-08, Last modification date: 2024-02-07)

Primary citation

Aleshin, A.E.,Kirby, C.,Liu, X.,Bourenkov, G.P.,Bartunik, H.D.,Fromm, H.J.,Honzatko, R.B.
Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation.
J.Mol.Biol., 296:1001-1015, 2000

PubMed Abstract: 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.

PubMed: 10686099
DOI: 10.1006/jmbi.1999.3494

Experimental method

X-RAY DIFFRACTION (2.8 Å)