Hexokinase (EC 18.104.22.168) [1,2] is an important glycolytic enzyme that catalyzes
the phosphorylation of keto- and aldohexoses (e.g. glucose, mannose and
fructose) using MgATP as the phosphoryl donor.
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
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.
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