Protein prenyltransferases catalyze the transfer of the carbon moiety of C15 farnesyl pyrophosphate or geranylgeranyl pyrophosphate synthase to a conserved cysteine residue in a CaaX motif of protein and peptide substrates. The addition of a farnesyl group is required to anchor proteins to the cell membrane. In the 3D structure of a mammalian Ras farnesyltransferases (Ftase), both subunits are largely composed of alpha-helices. The alpha-2 to alpha-15 helices in the alpha subunit fold into a novel helical hairpin structure, resulting in a crescent-shape domain that envelopes part of the subunit. The 12 helices of the beta-subunit form an alpha-alpha barrel. Six additional helices connect the inner core of helices and form the outside of the helical barrel. A deep cleft surrounded by hydrophobic amino acids in the centre of the barrel is proposed as the FPP-binding pocket. A single Zn2+ ion is located at the junction between the hydrophilic surface groove near the subunit interface

Terpenoid cyclases such as squalene cyclase, pentalenene synthase, 5-epi-aristolochene synthase, and trichodiene synthase are responsible for the synthesis of cholesterol, a hydrocarbon precursor of the pentalenolactone family of antibiotics, a precursor of the antifungal phytoalexin capsidiol, and the precursor of antibiotics and mycotoxins, respectively. In the structures of these three enzymes, the similar structural feature referred to as 'terpenoid synthase fold' with 10-12 mostly antiparallel alpha-helices is found, as also observed in protein prenyltransferases. The high structural similarity provides support for the hypothesis that the three families of prenyltransferases have related evolution despite their low sequence similarity [1].

1. Structure, mechanism and function of prenyltransferases. Eur. J. Biochem. 269, 3339-54

Protein prenyltransferases catalyze the transfer of the carbon moiety of C15 farnesyl pyrophosph
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