The enzyme-catalysed transfer of a
phosphoryl group from
ATP is an important reaction in a wide variety of biological processes. Phosphofructokinase catalyses the phosphorylation of
fructose-6-phosphate to
fructose-1,6-bisphosphate, a key regulatory step in the
glycolytic pathway. It is
allosterically inhibited by ATP and allosterically activated by
AMP, thus indicating the cell's energetic needs when it undergoes the glycolytic pathway. PFK exists as a
homotetramer in
bacteria and
mammals (where each
monomer possesses 2 similar
domains) and as an octomer in
yeast (where there are 4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalian monomers, possessing 2 similar domains PFK is about 300
amino acids in length, and structural studies of the
bacterial enzyme have shown it comprises two similar (alpha/beta) lobes: one involved in ATP binding and the other housing both the substrate-binding site and the
allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme activity). The identical
tetramer subunits adopt 2 different conformations: in a 'closed' state, the bound
magnesium ion bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6-bisphosphate); and in an 'open' state, the magnesium ion binds only the
ADP, as the 2 products are now further apart. These
conformations are thought to be successive stages of a
reaction pathway that requires subunit closure to bring the 2 molecules sufficiently close to react. Other members of this family (also known as the Ribokinase family) include
ribokinase (RK),
adenosine kinase (AK),
inosine kinase, and
1-phosphofructokinase. The members of the PfkB/RK family are identified by the presence of three conserved sequence
motifs. The structures of several PfK family of proteins have been determined from a number of organisms and the
enzymatic activity of this family of protein shows a dependence on the presence of pentavalent ions. == Clinical significance ==