InterPro domain: IPR022953

The enzyme-catalysed transfer of a phosphoryl group from ATP is animportant reaction in a wide variety of biological processes [ 1 ]. Oneenzyme that utilises this reaction is phosphofructokinase (PFK), whichcatalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, a key regulatory step in the glycolytic pathway [ 2 , 3 ]. PFK exists as a homotetramer in bacteria and mammals (where each monomerpossesses 2 similar domains), and as an octomer in yeast (where there are4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalianmonomers, possessing 2 similar domains [ 4 ]).

PFK is ~300 amino acids in length, and structural studies of thebacterial enzyme have shown it comprises two similar (alpha/beta) lobes: one involved inATP 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 enzymeactivity). The identical tetramer subunits adopt 2 different conformations: in a 'closed' state, the bound magnesium ionbridges 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[ 4 ], as the 2 products are now further apart. These conformations arethought to be successive stages of a reaction pathway that requires subunitclosure to bring the 2 molecules sufficiently close to react [ 5 ].

Deficiency in PFK leads to glycogenosis type VII (Tauri's disease), anautosomal recessive disorder characterised by severe nausea, vomiting,muscle cramps and myoglobinuria in response to bursts of intense orvigorous exercise [ 5 ]. Sufferers are usually able to lead a reasonablyordinary life by learning to adjust activity levels [ 5 ].

1. Mutations in the active site of Escherichia coli phosphofructokinase. Nature 327, 437-9
2. Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle. Biochem. Soc. Trans. 30, 264-70
3. Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency. Am. J. Hum. Genet. 56, 131-41
4. Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products. J. Mol. Biol. 204, 973-94