Geranylgeranyl

Geranylgeranyl is a 20-carbon isoprenoid moiety derived from geranylgeranyl pyrophosphate (GGPP). It is a hydrophobic lipid group that serves as a substrate for protein prenylation and as a structural component in various isoprenoid biosynthetic pathways.

Biosynthesis and chemical context: In cells, isoprenoid precursors are built from dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). These units are condensed to form farnesyl pyrophosphate (FPP), which can be extended by geranylgeranyl pyrophosphate synthase to produce GGPP. GGPP serves as the donor of the geranylgeranyl group in post-translational modification of proteins, a process known as prenylation.

Protein prenylation and enzymes: Geranylgeranylation is catalyzed by two classes of prenyltransferases. Geranylgeranyltransferase I (GGTase I) attaches a single geranylgeranyl group to proteins with a CaaX motif at their C-terminus, with the X residue influencing the type of modification. Geranylgeranyltransferase II (GGTase II), also known as Rab geranylgeranyltransferase, attaches two geranylgeranyl groups to Rab family GTPases that present CC or CXC motifs, promoting stable association with cellular membranes.

Biological and medical relevance: Prenylation, including geranylgeranylation, modulates the localization and function of a broad set of signaling proteins. Inhibitors of GGTase I and II have been investigated as potential anti-cancer agents, though clinical outcomes have been varied. Beyond protein modification, geranylgeranyl groups appear in various diterpenoid biosynthetic pathways and related natural products.

In chemistry, the geranylgeranyl group is often referred to as a hydrophobic tail that anchors proteins or participates in biosynthetic steps, and it can be liberated by hydrolysis to yield geranylgeraniol.