Geranylgeranyltransferases

Lane KT, Beese LS (2006) Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res 47 681-699... 

Taylor JS et al (2003) Structure of mammalian protein geranylgeranyltransferase type-I. EMBO J 22(22) 5963—5974... 

Zhang H, Seabra MC, Deisenhofer J (2000) Crystal structure of Rab geranylgeranyltransferase at 2.0 angsttom resolution. Structure Fold Des 8(3) 241-251... 

Farnesyltransferase is a heterodimeric protein composed of an a- and a /1-sub-unit, and zinc and magnesium ions are required for its activity [7,8]. A closely related heterodimeric enzyme is geranylgeranyltransferase I (GGTase I). It also recognizes proteins with a CAAX-box when X is leucine. Both enzymes share the same a-subunit and the requirement for Zn2+ and Mg2+ but the /1-subunits are different. The similarity of these enzymes highlights the importance of selectivity of farnesyltransferase (FT)-inhibitors. 

Phytoene synthase [EC 2.5.1.32] (also known as gera-nylgeranyl-diphosphate geranylgeranyltransferase and prephytoene-diphosphate synthase) catalyzes the reaction of two geranylgeranyl diphosphate to produce pyrophosphate (or, diphosphate) and prephytoene diphosphate. Isopentenyl pyrophosphate isomerase [EC 5.3.3.2] catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate. See also Geranylgeranyl Diphosphate Geranylgeranyltransferase... 

DIMETHYLALLYLTRANSTRANSFERASE Geranylgeranyl diphosphate synthase, FARNESYLTRANSTRANSFERASE Geranylgeranyltransferases,... 

Peterson, Y. K., Wang, X. S., Casey, P. J., Tropsha, A. (2009) Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation. J Med Chem 52, 4210-4220. 

Nishimura S, Matsunaga S, Shibazaki M, Suzuki K, Furihata K, van Soest RWM, Fusetani N (2003) Massadine, a Novel Geranylgeranyltransferase Type I Inhibitor from the Marine Sponge Stylissa aff. massa. Org Lett 5 2255... 

Yokoyama, K., Goodwin, G.W., Ghomashchi, F., Glomset, J.A., and Gelb, M.H. (1991). A protein geranylgeranyltransferase from bovine brain implications for protein prenyla-tion specificity. Proc Natl Acad Sci USA 88 5302-5306. 

O Dwyer, P.J., Gallagher, M., Nguyen, B., Waddell, M.J., and Chiorean, E.J. (2010). Phase accelerated dose-escalating safety and pharmacokinetic study of GGTI-2419, a novel geranylgeranyltransferase I inhibitor, in patients with refractory solid tumors. Ann Oncol 21(Suppl. 2) ii42. 

Moomaw, J.F., and Casey, P.J. (1992). Mammalian protein geranylgeranyltransferase. Subunit composition and metal requirements. J Biol Chem 267 17438-17443. 

Yokoyama, K., Zimmerman, K., Scholten, J., and Gelb, M.H. (1997). Differential prenyl pyrophosphate binding to mammalian protein geranylgeranyltransferase-I and protein farnesyltransferase and its consequence on the specificity of protein prenylation. J Biol Chem 272 3944-3952. 

Zhang, F.L., and Casey, P.J. (1996). Inflnence of metal ions on substrate binding and catalytic activity of mammahan protein geranylgeranyltransferase type-I. Biochem J 320 (Pt 3) 925-932. 

Seabra, M.C., Reiss, Y., Casey, P.J., Brown, M.S., and Goldstein, J.L. (1991). Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell 65 429-434. 

Finegold, A. A., et al. (1991). Protein geranylgeranyltransferase of Saccharomyces cerevi-siae is specific for Cys-Xaa-Xaa-Leu motif proteins and requires the CDC43 gene product but not the DPRl gene product. Proc Natl Acad Sci USA 88 4448-4452. 

Zhang, F.L., et al. (1994). cDNA cloning and expression of Rat and human protein geranylgeranyltransferase type-I. J Biol Chem 269 3175-3180. 

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