Limits...
Protein prenyltransferases.

Maurer-Stroh S, Washietl S, Eisenhaber F - Genome Biol. (2003)

Bottom Line: The genes encoding CaaX protein prenyltransferases are considerably longer than those encoding non-CaaX subunits, as a result of longer introns.Alternative splice forms are predicted to occur, but the extent to which each splice form is translated and the functions of the different resulting isoforms remain to be established.The effects of these inhibitors are complicated, however, by the overlapping substrate specificities of geranylgeranyltransferase I and farnesyltransferase.

View Article: PubMed Central - HTML - PubMed

Affiliation: Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria. stroh@imp.univie.ac.at

ABSTRACT

Summary: Three different protein prenyltransferases (farnesyltransferase and geranylgeranyltransferases I and II) catalyze the attachment of prenyl lipid anchors 15 or 20 carbons long to the carboxyl termini of a variety of eukaryotic proteins. Farnesyltransferase and geranylgeranyltransferase I both recognize a 'Ca1a2X' motif on their protein substrates; geranylgeranyltransferase II recognizes a different, non-CaaX motif. Each enzyme has two subunits. The genes encoding CaaX protein prenyltransferases are considerably longer than those encoding non-CaaX subunits, as a result of longer introns. Alternative splice forms are predicted to occur, but the extent to which each splice form is translated and the functions of the different resulting isoforms remain to be established. Farnesyltransferase-inhibitor drugs have been developed as anti-cancer agents and may also be able to treat several other diseases. The effects of these inhibitors are complicated, however, by the overlapping substrate specificities of geranylgeranyltransferase I and farnesyltransferase.

Show MeSH
The complete structure of rat FT (PDB identifier 1D8D [70]). The spheres in the center represent the farnesyl-pyrophosphate and Zn2+, and the amino acids in stick representation are the CaaX motif of the protein substrate. The molecular representation was created using VMD [69].
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC154572&req=5

Figure 3: The complete structure of rat FT (PDB identifier 1D8D [70]). The spheres in the center represent the farnesyl-pyrophosphate and Zn2+, and the amino acids in stick representation are the CaaX motif of the protein substrate. The molecular representation was created using VMD [69].

Mentions: The CaaX prenyltransferases FT and GGT1 and the non-CaaX prenyltransferase GGT2 share the same heterodimeric structure [1] (Figure 3). In the α subunits of both types of protein prenyltransferases, seven tetratricopeptide repeats are formed by pairs of helices (helices 2 to 15) that are stabilized by conserved intercalating residues. The α subunits of GGT2 in mammals and plants also have an immunoglobulin-like domain between the fifth and sixth tetratricopeptide repeat, as well as leucine-rich repeats at the carboxyl terminus. The functions of these additional domains in GGT2 are as yet undefined, but they are apparently not directly involved in the interaction with substrates and Rab escort proteins (see below) [18,19]. The tetratricopeptide repeats of the α subunit form a right-handed superhelix, which embraces the (α-α)6 barrel of the β subunit [20]. The β subunits include most of the substrate- and lipid-binding pockets [20] and their tight association with the respective α subunits is required for proper function [21]. Compared with FT, GGT2 has a larger hydrophobic pocket in the β subunit to accommodate the longer lipid [22].


Protein prenyltransferases.

Maurer-Stroh S, Washietl S, Eisenhaber F - Genome Biol. (2003)

The complete structure of rat FT (PDB identifier 1D8D [70]). The spheres in the center represent the farnesyl-pyrophosphate and Zn2+, and the amino acids in stick representation are the CaaX motif of the protein substrate. The molecular representation was created using VMD [69].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC154572&req=5

Figure 3: The complete structure of rat FT (PDB identifier 1D8D [70]). The spheres in the center represent the farnesyl-pyrophosphate and Zn2+, and the amino acids in stick representation are the CaaX motif of the protein substrate. The molecular representation was created using VMD [69].
Mentions: The CaaX prenyltransferases FT and GGT1 and the non-CaaX prenyltransferase GGT2 share the same heterodimeric structure [1] (Figure 3). In the α subunits of both types of protein prenyltransferases, seven tetratricopeptide repeats are formed by pairs of helices (helices 2 to 15) that are stabilized by conserved intercalating residues. The α subunits of GGT2 in mammals and plants also have an immunoglobulin-like domain between the fifth and sixth tetratricopeptide repeat, as well as leucine-rich repeats at the carboxyl terminus. The functions of these additional domains in GGT2 are as yet undefined, but they are apparently not directly involved in the interaction with substrates and Rab escort proteins (see below) [18,19]. The tetratricopeptide repeats of the α subunit form a right-handed superhelix, which embraces the (α-α)6 barrel of the β subunit [20]. The β subunits include most of the substrate- and lipid-binding pockets [20] and their tight association with the respective α subunits is required for proper function [21]. Compared with FT, GGT2 has a larger hydrophobic pocket in the β subunit to accommodate the longer lipid [22].

Bottom Line: The genes encoding CaaX protein prenyltransferases are considerably longer than those encoding non-CaaX subunits, as a result of longer introns.Alternative splice forms are predicted to occur, but the extent to which each splice form is translated and the functions of the different resulting isoforms remain to be established.The effects of these inhibitors are complicated, however, by the overlapping substrate specificities of geranylgeranyltransferase I and farnesyltransferase.

View Article: PubMed Central - HTML - PubMed

Affiliation: Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria. stroh@imp.univie.ac.at

ABSTRACT

Summary: Three different protein prenyltransferases (farnesyltransferase and geranylgeranyltransferases I and II) catalyze the attachment of prenyl lipid anchors 15 or 20 carbons long to the carboxyl termini of a variety of eukaryotic proteins. Farnesyltransferase and geranylgeranyltransferase I both recognize a 'Ca1a2X' motif on their protein substrates; geranylgeranyltransferase II recognizes a different, non-CaaX motif. Each enzyme has two subunits. The genes encoding CaaX protein prenyltransferases are considerably longer than those encoding non-CaaX subunits, as a result of longer introns. Alternative splice forms are predicted to occur, but the extent to which each splice form is translated and the functions of the different resulting isoforms remain to be established. Farnesyltransferase-inhibitor drugs have been developed as anti-cancer agents and may also be able to treat several other diseases. The effects of these inhibitors are complicated, however, by the overlapping substrate specificities of geranylgeranyltransferase I and farnesyltransferase.

Show MeSH