InterPro domain: IPR033904

Trans-Isoprenyl Diphosphate Synthases (Trans_IPPS) catalyze a head-to-head (HH) (1'-1) condensation reaction [ 1 ]. This entry includes squalene and phytoene synthases which catalyze the 1'-1 condensation of two 15-carbon (farnesyl) and 20-carbon (geranylgeranyl) isoprenyl diphosphates, respectively [ 2 , 3 , 4 , 5 ],. The catalytic site consists of a large central cavity formed by mostly antiparallel alpha helices with two aspartate-rich regions (DXXXD) located on opposite walls [ 6 ]. These residues mediate binding of prenyl phosphates [ 7 ]. A two-step reaction has been proposed for squalene synthase (farnesyl-diphosphate farnesyltransferase) in which, two molecules of FPP react to form a stable cyclopropylcarbinyl diphosphate intermediate, and then the intermediate undergoes heterolysis, isomerization, and reduction with NADPH to form squalene, a precursor of cholestrol. The carotenoid biosynthesis enzyme, phytoene synthase (CrtB), catalyses the condensation reaction of two molecules of geranylgeranyl diphosphate to produce phytoene, a precursor of beta-carotene [ 8 ]. These enzymes produce the triterpene and tetraterpene precursors for many diverse sterol and carotenoid end products and are widely distributed among eukaryota, bacteria, and archaea [ 9 ].

This entry represents a domain found in Trans-Isoprenyl Diphosphate Synthases.

1. Isoprenyl diphosphate synthases. Biochim. Biophys. Acta 1529, 33-48
2. Isoprenyl diphosphate synthases: protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure. Protein Sci. 3, 600-7
3. Structure and regulation of mammalian squalene synthase. Biochim. Biophys. Acta 1529, 49-62
4. Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution. Trends Biochem. Sci. 24, 445-51
5. Chain elongation in the isoprenoid biosynthetic pathway. Curr Opin Chem Biol 1, 570-8
6. Conversion from archaeal geranylgeranyl diphosphate synthase to farnesyl diphosphate synthase. Two amino acids before the first aspartate-rich motif solely determine eukaryotic farnesyl diphosphate synthase activity. J. Biol. Chem. 272, 5192-8
7. Structure, mechanism and function of prenyltransferases. Eur. J. Biochem. 269, 3339-54
8. Biosynthesis of carotenoids in plastids of plants. Biochemistry Mosc. 65, 1113-28
9. Genetics of eubacterial carotenoid biosynthesis: a colorful tale. Annu. Rev. Microbiol. 51, 629-59