1hkb: Difference between revisions
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==Overview== | ==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, ... | 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== | ==About this Structure== | ||
1HKB is a | 1HKB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GLC, G6P and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Sites: 6CA, 6CB, 6NA, 6NB, GCA, GCB, GNA, GNB, MCA, MCB, MNA and MNB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HKB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: phosphotransferase]] | [[Category: phosphotransferase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:46:53 2007'' | ||
