Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I.

摘要: More than 100 proteins necessary for eukaryotic cell growth, differentiation, and morphology require posttranslational modification by the covalent attachment of an isoprenoid lipid (prenylation). Prenylated include members Ras, Rab, Rho families, lamins, CENPE CENPF, γ subunit many small heterotrimeric G proteins. This is catalyzed protein prenyltransferases: farnesyltransferase (FTase), geranylgeranyltransferase type I (GGTase-I), GGTase-II (or RabGGTase). In this review, we examine structural biology FTase GGTase-I (the CaaX prenyltransferases) to establish a framework understanding molecular basis substrate specificity mechanism. These enzymes have been identified in number species, including mammals, fungi, plants, protists. Prenyltransferase structures complexes that represent major steps along reaction path, as well with clinically relevant inhibitors. Such may assist design inhibitors could lead treatments cancer, viral infection, deadly parasitic diseases.