Isopentenyl-diphosphate Delta-isomerase (IPP isomerase)

Isopentenyl-diphosphate Delta-isomerase (commonly abbreviated IPP isomerase) is a critical enzyme in both the mevalonate and MEP pathways for the biosynthesis of isoprenoids, a diverse class of molecules essential for cell viability in all domains of life. The enzyme catalyzes the reversible isomerization of isopentenyl pyrophosphate (IPP) to the highly reactive electrophile dimethylallyl pyrophosphate (DMAPP), a necessary step allowing elongation of isoprenoid chains and the biosynthesis of carotenoids, sterols, quinones, and other molecules. Both type 1 (metal-dependent, Nudix hydrolase fold) and type 2 (FMN- and NAD(P)H-dependent) forms exist, notably differing in mechanism and distribution between eukaryotes and many essential bacteria. Human isoforms are encoded by the genes IDI1 and IDI2. Because of its essential role and mechanistic divergence between human and bacterial isoforms, IPP isomerase is a promising but as yet unexploited target for antimicrobial drug discovery, especially against certain Gram-positive bacteria. While not directly linked to human disease, genomic studies suggest its possible involvement in neurodegenerative conditions such as ALS.

Other names

Isopentenyl pyrophosphate isomeraseIsopentenylpyrophosphate Delta-isomeraseMethylbutenylpyrophosphate isomeraseDimethylallyl pyrophosphate isomeraseIDIIDI1IDI2

Catalytic isomerization of isopentenyl pyrophosphate (IPP) to dimethylallyl pyrophosphate (DMAPP) via a carbocationic (carbonium ion) intermediate; inhibition can be achieved by transition state analogues or substrate analogues acting as competitive inhibitors