Isopentenyl diphosphate isomerase

Isopentenyl diphosphate isomerase catalyzes the isomerization of isopentenyl diphosphate to dimethylallyl diphosphate (Equation (6))  

These two compounds constitute the basic building blocks of isoprenoids, a family of compounds that is extraordinarily diverse in structure and function. The enzyme requires one Mn  

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KAJIWARA s, FRASER p D, KONDO K and MISAWA N (1997) Expressiou of an exogenous isopentenyl diphosphate isomerase gene enhances isoprenoid biosynthesis in Escherichia coli Biochem J, 324, 421-6. 

Cunningham, EX. Jr. and Gantt, E., Identification of multi-gene families encoding isopentenyl diphosphate isomerase in plants by heterologous complementation in Escherichia coli. Plant Cell Physiol. 41, 119, 2000. 

Figure 9.4 Monoterpene biosynthesis in peppermint oil gland secretory cells. The enzymes involved in this pathway are (1) 1-deoxy-D-xylulose 5-phosphate synthase, (2) 2-C-methyl-D-erythritol 4-phosphate reductoisomerase, (3) 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase, (4) 4-(cytidine 5 -diphospho)-2-C-methyl-D-erythritol kinase, (5) 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, (6) isopentenyl diphosphate isomerase, (7) geranyl diphosphate synthase, (8)...

Figure 28 Active site of the isopentenyl diphosphate isomerase enzyme from E. coli. In the crystals studied by Bonanno et al. the bidentate glutamate is monodentate and the Mn has a distorted square pyramidal geometry.

Recently Fujiwara et al. reported on the in vitro polymerization of trans-polyisoprene using the enzymes isopentenyl diphosphate isomerase (IDI) and fra 3-isoprenyl diphosphate synthase (IDS) [271]. IDI catalyzes the interconversion of IPP and DMAPP. IDS can now catalyze the polymerization of IPP from DMAPP as outlined above for the synthesis of natural rubber, and as outlined in Fig. 13a. However, the condensation process is inhibited due to hydrophobic interaction between IDS and hydrocarbon of the longer products. The hydrophobic chain of the elongating product does not readily protrude into the aqueous phase and it tends to interact with the enzyme. To achieve an efficient in vitro synthesis, the authors used an organic-aqueous two-liquid phase system to successfully synthesize (low molecular weight) fran.y-polyisoprene (see Fig. 13b). 

Phillips, M.A., D Auria, J.C., Gershenzon, J. and Pichersky, E. (2008) The Arabidopsis thaliana type I Isopentenyl Diphosphate Isomerases are targeted to multiple sub-cellular compartments and have overlapping functions in isoprenoid biosynthesis. Plant Cell, 20, 677-96. 

Ramosvaldivia, A.C., Vanderheijden, R. and Verpoorte, R. (1997a) Elicitor-mediated induction of anthraquinone biosynthesis and regulation of isopentenyl diphosphate isomerase and famesyl diphosphate synthase activities in cell suspension cultures of Cinchona robusta How. Planta, 203, 155-61. 

Isopentenyl diphosphate isomerase (IPI E.C. 5.3.3.2) catalyzes the isomerization of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMADP), a previous and mandatory step to create the electrophilic allylic diphosphates needed for the condensation reaction generating geranyl diphosphate, Fig. (6). Thus, IPI is an essential enzyme in organisms which synthesize IPP through the mevalonic acid pathway as archaea, eukaryota and some Gram-positive bacteria [275, 305]. 

A. C. Ramos-Valdivia. Characterization of isopentenyl diphosphate isomerase. A regulatory enzyme in Cinchona isoprenoid biosynthesis. Ph.D. Thesis. Leiden University, 1996. 

Gresh N, Audiffren N, Piquemal JP, de Ruyck J, Ledecq M, Wouters J (2010) Analysis of the interactions taking place in the recognition site of a bimetallic Mg(II)-Zn(II) enzyme, isopentenyl diphosphate isomerase. A parallel quantum-chemical and polarizable molecular mechanics study. J Phys Chem B 114 4884... 

In the presence of the enzyme isopentenyl diphosphate isomerase, isopentenyl diphosphate is converted to dimethylallyl diphosphate. The isomerization involves two successive proton transfers one from an acidic site of the enzyme (Enz—H) to the double bond to give a tertiary carbocation the other is deprotonation of the carbocation by a basic site of the enzyme to generate the double bond of dimethylallyl diphosphate. 

Then (Scheme 11.41) mevalonate [(l )-3,5-dihydroxy-3-methylpentanoic acid] is phosphorylated by the enzyme mevalonate kinase (EC 2.7.1.36) at the primary hydroxyl. The phosphate that is added is obtained (an addition-elimination reaction or a displacement reaction) from the terminal phosphate group of ATP forming ADP in turn. Another phosphorylation, again using ATP yields mevalonate diphosphate, this time by the enzyme phosphomevalonate kinase (EC 2.7.4.2) and then, after one more phosphorylation, this time on the tertiary hydroxyl, decarboxylation and dehydration co-occur, catalyzed by the enzyme mevalonate diphosphate decarboxylase (EC 4.1.1.43). The products are inorganic phosphate, carbon dioxide, and isopentenyl diphosphate (diphosphoric acid mono[3-methylbut-3-enyl] ester). Isopentenyl diphosphate isomerase (EC S.3.3.2) catalyzes the isomerization, via loss of the C2 pro-R hydrogen, between isopentenyl diphosphate and dimethylallyl diphosphate. 

Berthelot, K., Estevez., and A., Deffieux. 2012. Isopentenyl diphosphate isomerase A checkpoint to isoprenoid biosynthesis . Biochimie. 94(8) 1621-34. 

Koyama, T., and Ogura, K. (1999) Isopentenyl diphosphate isomerase and prenyltransferases. In Comprehensive Natural Product Chemistry. Isoprenoids Including Carotenoids and Steroids (Cane, D.E., ed), 69-96, Peigamon, Oxford... 

The isopentenyl diphosphate isomerase, which catalyses the equilibrium between IPP and dimethylallyl diphosphate (DMAPP) was purified 200 fold to near homogenity 1. Analysis of the preparation by SDS-PAGE revealed two protein bands with values of 32,000 and 28,000, which are similar to those reported from other plant sources. Other properties of the partially... 

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