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- *************************************
- * Polyprenyl synthetases 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
- synthetase 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 synthetase (FPP synthetase) (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
- synthetase is a cytoplasmic dimeric enzyme.
- - Prokaryotic farnesyl pyrophosphate synthetase (gene ispA).
- - Eukaryotic geranylgeranyl pyrophosphate synthetase (GGPP synthetase)
- (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 synthetase, 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 synthetase, 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 synthetase is a mitochondrial
- membrane-associated enzyme.
-
- It has been shown [1 to 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.
-
- Two possible additional members of this family of proteins are:
-
- - Escherichia coli hypothetical protein yhbD.
- - Bacillus subtilis spore germination protein C3 (gene gerC3).
-
- We believe [6] that both proteins are most probably also enzymes involved in
- isoprenoid metabolism.
-
- -Consensus pattern: [LIVM](2)-x-D-D-x(2,4)-D-x(4)-R-R-G
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Consensus pattern: [LIVMFY]-G-x(2)-[FY]-Q-[LIVM]-x-D-D-[LIVMFY]-x-[DN]
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Last update: October 1993 / Patterns and text revised.
-
- [ 1] Ashby M.N., Edwards P.A.
- J. Biol. Chem. 265:13157-13164(1990).
- [ 2] Fujisaki S., Hara H., Nishimura Y., Horiuchi K., Nishino T.
- J. Biochem. 108:995-1000(1990).
- [ 3] Carattoli A., Romano N., Ballario P., Morelli G., Macino G.
- J. Biol. Chem. 266:5854-5859(1991).
- [ 4] Kuntz M., Roemer S., Suire C., Hugueney P., Weil J.H., Schantz R.,
- Camara B.
- Plant J. 2:25-34(1992).
- [ 5] Math S.K., Hearst J.E., Poulter C.D.
- Proc. Natl. Acad. Sci. U.S.A. 89:6761-6764(1992).
- [ 6] Bairoch A.
- Unpublished observations (1993).
-