Prenyl diphosphate

This enzyme [EC 2.5.1.1] (also referred to as prenyl-transferase and geranyl-diphosphate synthase) catalyzes the reaction of dimethylallyl diphosphate and isopen-tenyl diphosphate to produce geranyl diphosphate and pyrophosphate (or, diphosphate). The enzyme will not accept larger prenyl diphosphates as substrates. 

Prenyltransferases are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to prenyl diphosphate synthases (even though the class of prenyl transferases also includes enzymes that catalyze the transfer of prenyl groups to acceptors that include not only isopentenyl diphosphate (IPP) but also aromatic compounds and proteins etc.). 

The reactions catalyzed by prenyltransferases are unique and interesting from a mechanistic viewpoint. The reaction starts with elimination of the diphosphate ion from an allylic diphosphate (APP) to form an allylic cation, which is attacked by the IPP molecule, with stereospecific removal of a proton to form a new C-C bond and a new double bond in the product. By repeating this type of condensation between IPP and the allylic prenyl diphosphate product, prenyltransferase can synthesize a prenyl diphosphate with a certain length and stereochemistry fixed by ifs specificify (seeFig. 10) [252]. 

PQQ See Pyrroloquinoline quinone Preproteins 519-522. See also Proenzyme(s) peroxisomal 521 Precursor activation 540 Prenatal diagnosis 26 Prenyl diphosphate (pyrophosphate) 390s Prenylation 402... 

A series of poly prenyl diphosphates was formed when EDTA-treated cells of Acetobacter xylinum were incubated with glycosyl nucleotides. The most complicated of them is the heptasaccharide derivative344 (32), which is considered to be an intermediate in the biosynthesis of the exocellular... 

Synthetic derivatives and analogs of prenyl diphosphates have historically played a key role in defining key featnres of the mechanism of enzymes that ntilize these key intermediates in the isoprenoid pathway. This has also been the case with the investigation of the protein prenyl-transferases. A brief introduction to the protein prenyltransferase enzymes is given along with outlines on the previous use of prenyl diphosphate tools and key aspects of their synthesis. The development of prenyl diphosphate-based FTase inhibitors is described. The use of prenyl diphosphate derivatives as mechanistic and structural probes is next discussed. In particular, the use of fluorinated, isotopically labeled, and photoaffinity derivatives is presented. An overview of the extensive work on the determination of FTase isoprenoid substrate specificity is then given, and the chapter concludes with a section on the development of prenyl diphosphate tools for proteomic studies. 

Bukhtiyarov, Y.E., Omer, C.A., and Allen, C.M. (1995). Photoreactive analogs of prenyl diphosphates as inhibitors and probes of hnman farnesyltransferase and geranylgeranyl-transferase type I. J Biol Chem 270 19035-19040. 

Turek, T.C., Gaon, L, Distefano, M.D., and Strickland, C.L. (2001). Synthesis of farnesyl diphosphate analogues containing ether-linked photoactive benzophenones and their application in studies of protein prenyltransferases. J Org Chem 66 3253-3264. Turek-Etienne, T.C., Strickland, C.L., and Distefano, M.D. (2003). Biochemical and structural studies with prenyl diphosphate analogues provide insights into isoprenoid recognition by protein farnesyl transferase. Biochemistry 42 3716-3724. 

Song, J, et al. (2011). A Novel and Efficient Alkyne-Prenyl Diphosphate Tag for Prote-omic Characterization of the Prenylome. To be submitted for publication. 

Figure 5.5 The formation of Cio, Ci j and C20 prenyl diphosphates from the fusion of Cj isoprenoid units. PP indicates a diphosphate moiety.

The prenyl diphosphates, GPP, FPP and GGPP, are the central intermediates of terpenoid bios)mthesis. Under the catalysis of monoterpene, sesquiterpene and diterpene synthases, respectively, these substances are transformed into... 

Hemiterpenoids are produced from the isoprenyl diphosphate DMAPP. All other terpenoids are produced from DMAPP and IPP via longer-chain prenyl diphosphate intermediates formed by prenyl transferases. Prenyl transferases (20) catalyze the formation of geranyl diphosphate (GPP), famesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) from one molecule of DMAPP and one, two, or three molecules of IPP, respectively (Fig. 1). Isoprenyl diphosphates are the substrates for all TPS, which lead to the hemiterpenoids, monoterpenoids, sesquiterpenoids, and diterpenoids, which will be highlighted with selected examples in the following sections. 

Finally, the dichotomy between the cytoplasmic mevalonate pathway and the plastidial MEP pathway is not strict. An exchange of metabolites occurs between the two compartments at the level of C5, Cio, and C15 prenyl diphosphates. The inhibition of one pathway (e.g., by mevinolin for the MVA pathway or by fosmidomycin for the MEP pathway) can be complemented by the other route either partially, as in most tested plant systems, or even completely, in the case of the tobacco Bright Yellow-2 cell cultures (20). In addition, a regulation of the two pathways... 

It can be assumed that this compound is formed during roasting from the biogenic precursor prenyl diphosphate, hydrogen sulfide and formic acid (Holscher et al., 1992). 

Before polyprenyl formation begins, one molecule of IPP must be isomerized to DMAPP. However, there is evidence that the pathways of prenyl diphosphate synthesis differ in prokaryotes and eukaryotes (Sandmann 2001). In Synechocystis and in E. coll, parallel synthesis of IPP and DMAPP has been found. 

All carotenoids are derived from the isoprenoid or terpenoid pathway. From prenyl diphosphates of different chain lengths, specific routes branch off into various terpenoid end products. The prenyl diphosphates are formed by different prenyl transferases after isomerization of IPP to DMAPP by successive T-4 condensations with IPP molecules. Condensation of one molecule of dimethylallyl diphosphate (DMADP) and three molecules of isopentyl diphosphate (IDP) produces the diter-pene geranylgeranyl diphosphate (GGDP) that forms one-half of all C40 carotenoids. The head-to-head condensation of two GGDP molecules results in the first colorless carotenoid, phytoene. Phytoene synthesis is the first committed step in C40 carotenoid biosynthesis (Britton et al. 1998, Sandmann 2001). 

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