|PROSITE documentation PDOC00370|
In vertebrates there are four major isoenzymes, commonly referred as types I, II, III and IV. Type IV hexokinase, which is often incorrectly designated glucokinase , is only expressed in liver and pancreatic β-cells and plays an important role in modulating insulin secretion; it is a protein of a molecular mass of about 50 Kd. Hexokinases of types I to III, which have low Km values for glucose, have a molecular mass of about 100 Kd. Structurally they consist of a very small N-terminal hydrophobic membrane-binding domain followed by two highly similar domains of 450 residues. The first domain has lost its catalytic activity and has evolved into a regulatory domain.
In yeast there are three different isoenzymes: hexokinase PI (gene HXK1), PII (gene HXKB), and glucokinase (gene GLK1). All three proteins have a molecular mass of about 50 Kd.
The hexokinase domain has an α/β fold and is distinctly folded in two subdomains of unequal size: the large and small subdomains (see <PDB:1IG8>). The large subdomain comprises a six-stranded mixed β-sheet and a number of additional α-helices. On one side, the sheet packs against the small subdomain, and on the other side it is shielded by several α-helices. The dominant feature of the small subdomain is a five stranded mixed β-sheet. The sheet is flanked by two helices on one side and by one helix on the other. The subdomain also has an additional β-sheet formed by two antiparallel strands [4,5].
All these enzymes contain one (or two in the case of types I to III isozymes) strongly conserved region which has been shown  to be involved in substrate binding. We have derived a pattern from that region.Last update:
February 2015 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
|Title||Hexokinases and glucokinases.|
|Source||Biochem. Soc. Trans. 18:180-183(1990).|
|2||Authors||Griffin L.D. Gelb B.D. Wheeler D.A. Davison D. Adams V. McCabe E.R.|
|Title||Mammalian hexokinase 1: evolutionary conservation and structure to function analysis.|
|3||Authors||Cornish-Bowden A. Luz Cardenas M.|
|Source||Trends Biochem. Sci. 16:281-282(1991).|
|4||Authors||Kuser P.R. Krauchenco S. Antunes O.A. Polikarpov I.|
|Title||The high resolution crystal structure of yeast hexokinase PII with the correct primary sequence provides new insights into its mechanism of action.|
|Source||J. Biol. Chem. 275:20814-20821(2000).|
|5||Authors||Aleshin A.E. Zeng C. Bourenkov G.P. Bartunik H.D. Fromm H.J. Honzatko R.B.|
|Title||The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate.|
|6||Authors||Schirch D.M. Wilson J.E.|
|Title||Rat brain hexokinase: location of the substrate hexose binding site in a structural domain at the C-terminus of the enzyme.|
|Source||Arch. Biochem. Biophys. 254:385-396(1987).|