Understanding and Exploiting Protein Prenyltransferases

ChemBioChem ◽  
2010 ◽  
Vol 11 (9) ◽  
pp. 1194-1201 ◽  
Author(s):  
Uyen T. T. Nguyen ◽  
Roger S. Goody ◽  
Kirill Alexandrov
Keyword(s):  
Protein Prenyltransferases

Genetic evidence for in vivo cross-specificity of the CaaX-box protein prenyltransferases farnesyltransferase and geranylgeranyltransferase-I in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (7) ◽  
pp. 4260-4275
Author(s):  
C E Trueblood ◽  
Y Ohya ◽  
J Rine
Keyword(s):  
Genetic Data ◽  
Yeast Cells ◽  
Covalent Attachment ◽  
Ras Proteins ◽  
Substrate Preferences ◽  
Geranylgeranyltransferase I ◽  
Altered Form ◽  
Protein Prenyltransferases

Two protein prenyltransferase enzymes, farnesyltransferase (FTase) and geranylgeranyltransferase-I (GGTase-I), catalyze the covalent attachment of a farnesyl or geranylgeranyl lipid group to the cysteine of a CaaX sequence (cysteine [C], two aliphatic amino acids [aa], and any amino acid [X]. In vitro studies reported here confirm previous reports that CaaX proteins with a C-terminal serine are farnesylated by FTase and those with a C-terminal leucine are geranylgeranylated by GGTase-I. In addition, we found that FTase can farnesylate CaaX proteins with a C-terminal leucine and can transfer a geranylgeranyl group to some CaaX proteins. Genetic data indicate that FTase and GGTase-I have the same substrate preferences in vivo as in vitro and also show that each enzyme can prenylate some of the preferred substrates of the other enzyme in vivo. Specifically, the viability of yeast cells lacking FTase is due to prenylation of Ras proteins by GGTase-I. Although this GGTase-I dependent prenylation of Ras is sufficient for growth, it is not sufficient for mutationally activated Ras proteins to exert deleterious effects on growth. The dependence of the activated Ras phenotype on FTase can be bypassed by replacing the C-terminal serine with leucine. This altered form of Ras appears to be prenylated by both GGTase-I and FTase, since it produces an activated phenotype in a strain lacking either FTase or GGTase-I. Yeast cells can grow in the absence of GGTase-I as long as two essential substrates are overexpressed, but their growth is slow. Such strains are dependent on FTase for viability and are able to grow faster when FTase is overproduced, suggesting that FTase can prenylate the essential substrates of GGTase-I when they are overproduced.

The inhibition of protein prenyltransferases by oxygenated metabolites of limonene and perillyl alcohol

1995 ◽  
Vol 91 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Michael H. Gelb ◽  
Fuyuhiko Tamanoi ◽  
Kohei Yokoyama ◽  
Farideh Ghomashchi ◽  
Kenneth Esson ◽  
...  
Keyword(s):  
Perillyl Alcohol ◽  
Protein Prenyltransferases

scholarly journals The CaaX specificities of Arabidopsis protein prenyltransferases explain era1 and ggb phenotypes

2010 ◽  
Vol 10 (1) ◽  
pp. 118 ◽  
Author(s):  
Michelle Andrews ◽  
David H Huizinga ◽  
Dring N Crowell
Keyword(s):  
Arabidopsis Protein ◽  
Protein Prenyltransferases

scholarly journals Genetic evidence for in vivo cross-specificity of the CaaX-box protein prenyltransferases farnesyltransferase and geranylgeranyltransferase-I in Saccharomyces cerevisiae.

1993 ◽  
Vol 13 (7) ◽  
pp. 4260-4275 ◽  
Author(s):  
C E Trueblood ◽  
Y Ohya ◽  
J Rine
Keyword(s):  
Genetic Data ◽  
Yeast Cells ◽  
Covalent Attachment ◽  
Ras Proteins ◽  
Substrate Preferences ◽  
Geranylgeranyltransferase I ◽  
Altered Form ◽  
Protein Prenyltransferases

Two protein prenyltransferase enzymes, farnesyltransferase (FTase) and geranylgeranyltransferase-I (GGTase-I), catalyze the covalent attachment of a farnesyl or geranylgeranyl lipid group to the cysteine of a CaaX sequence (cysteine [C], two aliphatic amino acids [aa], and any amino acid [X]. In vitro studies reported here confirm previous reports that CaaX proteins with a C-terminal serine are farnesylated by FTase and those with a C-terminal leucine are geranylgeranylated by GGTase-I. In addition, we found that FTase can farnesylate CaaX proteins with a C-terminal leucine and can transfer a geranylgeranyl group to some CaaX proteins. Genetic data indicate that FTase and GGTase-I have the same substrate preferences in vivo as in vitro and also show that each enzyme can prenylate some of the preferred substrates of the other enzyme in vivo. Specifically, the viability of yeast cells lacking FTase is due to prenylation of Ras proteins by GGTase-I. Although this GGTase-I dependent prenylation of Ras is sufficient for growth, it is not sufficient for mutationally activated Ras proteins to exert deleterious effects on growth. The dependence of the activated Ras phenotype on FTase can be bypassed by replacing the C-terminal serine with leucine. This altered form of Ras appears to be prenylated by both GGTase-I and FTase, since it produces an activated phenotype in a strain lacking either FTase or GGTase-I. Yeast cells can grow in the absence of GGTase-I as long as two essential substrates are overexpressed, but their growth is slow. Such strains are dependent on FTase for viability and are able to grow faster when FTase is overproduced, suggesting that FTase can prenylate the essential substrates of GGTase-I when they are overproduced.

scholarly journals Protein Prenyltransferases

1996 ◽  
Vol 271 (10) ◽  
pp. 5289-5292 ◽  
Author(s):  
Patrick J. Casey ◽  
Miguel C. Seabra
Keyword(s):  
Protein Prenyltransferases
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