PROSITE documentation PDOC00407

Polyprenyl synthases signatures

A variety of isoprenoid compounds are synthesized by various organisms. For example in eukaryotes the isoprenoid biosynthetic pathway is responsible for the synthesis of a variety of end products including cholesterol, dolichol, ubiquinone or coenzyme Q. In bacteria this pathway leads to the synthesis of isopentenyl tRNA, isoprenoid quinones, and sugar carrier lipids. Among the enzymes that participate in that pathway, are a number of polyprenyl synthase enzymes which catalyze a 1'4-condensation between 5 carbon isoprene units.

Currently the sequence of some of these enzymes is known:

• Eukaryotic farnesyl pyrophosphate synthase (FPP synthase) (EC 2.5.1.1 / EC 2.5.1.10) which catalyzes the sequential condensation of isopentenyl pyrophosphate (IPP) with dimethylallyl pyrophosphate (DMAPP), and then with the resultant geranyl pyrophosphate to form farnesyl pyrophosphate. FPP synthase is a cytoplasmic dimeric enzyme.
• Prokaryotic farnesyl pyrophosphate synthase (gene ispA).
• Prokaryotic octaprenyl diphosphate synthase (gene ispB).
• Prokaryotic heptaprenyl diphosphate synthase (EC 2.5.1.30).
• Eukaryotic geranylgeranyl pyrophosphate synthase (GGPP synthase) (EC 2.5.1.1 / EC 2.5.1.10 / EC 2.5.1.29) which catalyzes the sequential addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate. In plants GGPP synthase is a chloroplast enzyme involved in the biosynthesis of terpenoids; in fungi, such as Neurospora crassa (gene al-3), this enzyme is involved in the biosynthesis of carotenoids.
• Prokaryotic GGPP synthase, which are involved in the biosynthesis of carotenoids (gene crtE). Such an enzyme is also encoded in the cyanelle genome of Cyanophora paradoxa.
• Eukaryotic hexaprenyl pyrophosphate synthase, which is involved in the biosynthesis of coenzyme Q and which catalyzes the formation of all trans- polyprenyl pyrophosphates generally ranging in length of between 6 and 10 isoprene units depending on the species. HP synthase is a mitochondrial membrane-associated enzyme.

It has been shown [1,2,3,4,5] that all the above enzymes share some regions of sequence similarity. Two of these regions are rich in aspartic-acid residues and could be involved in the catalytic mechanism and/or the binding of the substrates. We have developed signature patterns for both regions.

Possible additional members of this family of proteins are:

• Bacillus subtilis spore germination protein C3 (gene gerC3).

We believe [6] that both proteins are most probably also enzymes involved in isoprenoid metabolism.