Protein geranylgeranyltransferase

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

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. 

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. 

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. 

Stirtan, W.G., and Poulter, C.D. (1995). Yeast protein geranylgeranyltransferase type I overproduction, purification, and characterization. Arch Biochem Biophys 321 182-190. 

Peng, H., Carrico, D., Thai, V., Blaskovich, M., Bucher, C., Pusateri, E.E., Sebti, S.M., and Hamilton, A.D. (2006). Synthesis and evaluation of potent, highly-selective, 3-aryl-piper-azinone inhibitors of protein geranylgeranyltransferase-I. OrgBiomol Chem 4 1768-1784. 

Watanabe, M., Fiji, H.D., Guo, L., Chan, L., Kinderman, S.S., Slamon, D.J., Kwon, O., and Tamanoi, F. (2008). Inhibitors of protein geranylgeranyltransferase 1 and Rab ger-anylgeranyltransferase identified from a hbraty of allenoate-derived compounds. J Biol Chem 283 9571-9579. 

The first step of the series of modifications involved in the processing of CAAX-type prenyl proteins occurs in the cytoplasm, catalyzed by either protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I (GGTase-I). The specificity for either of these two enzymes for the most part depends on the identity of the last amino acid X of the CAAX consensus sequence. When X is serine, cysteine, alanine, or glutamine, the 15 carbon farnesyl group is added to the cysteine catalyzed by FTase and when X is leucine, the 20 carbon geranylgeranyl group is added by... 

Figure 2. The mevalonic acid biosynthetic pathway. The transformation of hy-droxymethyl-coenzyme A (HMG-CoA) to mevalonic acid is the first committed step of the pathway. The enzyme, HMG-CoA reductase, catalyzes this step and is inhibited by the compounds, mevinolin and compactin. Note that farnesyl-pyrophosphate (Farnesyl-PP), the substrate of the protein, farnesyltransferase, can be used to make cholesterol or elongated to make geranylgeranyl-pyrophosphate (Geranylgeranyl-PP). The later compound is the substrate for the protein, geranylgeranyltransferase, or is further elongated to make the long-chain isoprenoids, dolichols, ubiquinones, and isoprenoic acids.

Yokoyama, K. Gelb, M. H. (1993). Purification of a mammalian protein geranylgeranyltransferase. J. Biol. Chem. 268,4055-4060. 

S, Q, A, or C, whereas GGTase-I recognizes CaaX boxes with X = L or F. Other prenylated proteins, such as the Rab proteins involved in vesicular transport, terminate in a CC, CXC, or CC(X) , 3 motif these proteins are substrates for protein geranylgeranyltransferase type II (GGTase-II) [3]. In order to be prenylated, Rab proteins must associate with Rab escort protein after geranylgeranylation, Rab escort protein delivers the prenylated Rab to membranes. 

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