1hkb: Difference between revisions

==Overview==

BACKGROUND: Hexokinase I is the pacemaker of glycolysis in brain tissue., The type I isozyme exhibits unique regulatory properties in that, physiological levels of phosphate relieve potent inhibition by the, product, glucose-6-phosphate (Gluc-6-P). The 100 kDa polypeptide chain of, hexokinase I consists of a C-terminal (catalytic) domain and an N-terminal, (regulatory) domain. Structures of ligated hexokinase I should provide a, basis for understanding mechanisms of catalysis and regulation at an, atomic level. RESULTS: The complex of human hexokinase I with glucose and, Gluc-6-P (determined to 2.8 A resolution) is a dimer with twofold, molecular symmetry. The N- and C-terminal domains of one monomer interact, with the C- and N-terminal domains, respectively, of the symmetry-related, monomer. The two domains of a monomer are connected by a single alpha, helix and each have the fold of yeast hexokinase. Salt links between a, possible cation-binding loop of the N-terminal domain and a loop of the, C-terminal domain may be important to regulation. Each domain binds single, glucose and Gluc-6-P molecules in proximity to each other. The, 6-phosphoryl group of bound Gluc-6-P at the C-terminal domain occupies the, putative binding site for ATP, whereas the 6-phosphoryl group at the, N-terminal domain may overlap the binding site for phosphate. CONCLUSIONS:, The binding synergism of glucose and Gluc-6-P probably arises out of the, mutual stabilization of a common (glucose-bound) conformation of, hexokinase I. Conformational changes in the N-terminal domain in response, to glucose, phosphate, and/or Gluc-6-P may influence the binding of ATP to, the C-terminal domain.

==About this Structure==

[[Category: phosphotransferase]]