D
IPR033904

Trans-isoprenyl diphosphate synthases, head-to-head

InterPro entry
Short nameTrans_IPPS_HH
Overlapping
homologous
superfamilies
 

Description

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

Trans-Isoprenyl Diphosphate Synthases (Trans_IPPS) catalyze a head-to-head (HH) (1'-1) condensation reaction
[3]
. 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
[8, 4, 6, 5]
. The catalytic site consists of a large central cavity formed by mostly antiparallel α helices with two aspartate-rich regions (DXXXD) located on opposite walls
[9]
. 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 cholesterol. 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
[1]
. 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
[2]
.

References

1.Biosynthesis of carotenoids in plastids of plants. Ladygin VG. Biochemistry Mosc. 65, 1113-28, (2000). PMID: 11092953

2.Genetics of eubacterial carotenoid biosynthesis: a colorful tale. Armstrong GA. Annu. Rev. Microbiol. 51, 629-59, (1997). View articlePMID: 9343362

3.Isoprenyl diphosphate synthases. Wang KC, Ohnuma S. Biochim. Biophys. Acta 1529, 33-48, (2000). View articlePMID: 11111076

4.Structure and regulation of mammalian squalene synthase. Tansey TR, Shechter I. Biochim. Biophys. Acta 1529, 49-62, (2000). View articlePMID: 11111077

5.Chain elongation in the isoprenoid biosynthetic pathway. Kellogg BA, Poulter CD. Curr Opin Chem Biol 1, 570-8, (1997). View articlePMID: 9667899

6.Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution. Wang K, Ohnuma S. Trends Biochem. Sci. 24, 445-51, (1999). View articlePMID: 10542413

7.Structure, mechanism and function of prenyltransferases. Liang PH, Ko TP, Wang AH. Eur. J. Biochem. 269, 3339-54, (2002). View articlePMID: 12135472

8.Isoprenyl diphosphate synthases: protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure. Chen A, Kroon PA, Poulter CD. Protein Sci. 3, 600-7, (1994). View articlePMID: 8003978

9.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. Ohnuma S, Hirooka K, Ohto C, Nishino T. J. Biol. Chem. 272, 5192-8, (1997). View articlePMID: 9030588

GO terms

biological process

  • None

cellular component

  • None

Cross References

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