2.5.1.58: protein farnesyltransferase
This is an abbreviated version!
For detailed information about protein farnesyltransferase, go to the full flat file.
Word Map on EC 2.5.1.58
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2.5.1.58
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farnesylation
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prenylation
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geranylgeranylation
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isoprenoids
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beta-subunits
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isoprenylation
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15-carbon
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lamins
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manumycin
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geranylgeranyltransferase-i
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farnesyl-protein
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h-ras
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medicine
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peptidomimetic
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prelamin
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ggtase-i
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p21ras
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tetrapeptide
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farnesol
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tetrahydroquinoline
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ras-dependent
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pharmacology
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progerin
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3hmevalonate
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ras-induced
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lovastatin
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tipifarnib
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drug development
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ras-mediated
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ras-transformed
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lonafarnib
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hutchinson-gilford
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dimethylallyl
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geranylgeraniol
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isoprene
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analysis
- 2.5.1.58
-
farnesylation
-
prenylation
-
geranylgeranylation
-
isoprenoids
- beta-subunits
-
isoprenylation
-
15-carbon
- lamins
- manumycin
-
geranylgeranyltransferase-i
-
farnesyl-protein
- h-ras
- medicine
-
peptidomimetic
-
prelamin
- ggtase-i
-
p21ras
- tetrapeptide
- farnesol
- tetrahydroquinoline
-
ras-dependent
- pharmacology
-
progerin
-
3hmevalonate
-
ras-induced
- lovastatin
- tipifarnib
- drug development
-
ras-mediated
-
ras-transformed
- lonafarnib
-
hutchinson-gilford
-
dimethylallyl
- geranylgeraniol
- isoprene
- analysis
Reaction
Synonyms
AfFTase, CAAX farnesyltransferase, EhFT, Era1, farnesyl protein transferase, farnesyltransferase, farnesyltransferase ternary complex part II, farnesyltransferase, farnesyl pyrophosphate-protein, farnesyltransferase, protein, FntA, FntB, FPT, fptase, FTase, hFTase, HIT5, Pf-PFT, PfPFT, PFT, PFTase, prenyl transferase, prenylprotein transferase, prenyltransferase, protein cysteine farnesyltransferase, protein farnesyl transferase, protein farnesyltransferase, protein prenyltransferase, protein-farnesyltransferase, R-PFT, Ram1, RAS farnesyltransferase, Ras protein farnesyltransferase, rFPTase, rFTase, rPFTase, TbFTase, yPFTase
ECTree
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Metals Ions
Metals Ions on EC 2.5.1.58 - protein farnesyltransferase
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Cd2+
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substitution of the active site zinc with cadmium increases the affinity of the peptide substrate and decreases the rate constant for the chemical step
Co2+
Mg2+
Mn2+
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in wild type FTase, Mg2+ can be replaced by Mn2+ with a 2-fold lower KMn2+ 2 mM
Zn2+
additional information
Co2+
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evidence for a catalytically relevant interaction between the metal ion and the protein substrate in the enzyme
Mg2+
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required, stabilizes the developing negative charge on the diphosphate as the bond breaks between the a-phosphate and the C1 atom of the farnesyl group
Mg2+
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the magnesium affinity of enzyme increases with pH with a pka of 7.4, presumably reflecting the deprotonation of the farnesyl diphosphate to enhance magnesium coordination
Mg2+
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magnesium is not required for formation of the thioether product but the presence increases the single-turnover rate constant by several orders of magnitude at saturating enzyme and substrate concentrations
Mg2+
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appears to coordinate the diphosphate moiety of farnesyl diphosphate
Mg2+
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enhances activity several hundred-fold, with a Km(Mg2+) value of 4 mM. Mg2+ coordinates the side chain carboxylate of Asp-beta352 and that the role of magnesium in the reaction includes positioning the FPP prior to catalysis. Mg2+ may accelerate catalysis both by stabilizing developing negative charge in the transition state and by stabilizing the active site conformation prior to catalysis
Mg2+
the addition of Mg2+ ions causes a conformational change in the enzyme's active site, breaking interactions known to keep farnesyl diphosphate in its inactive conformation. Wild-type protein shows relevant Mg2+ ion binding motifs. In the first binding motif, WT1, the Mg2+ ion is coordinated to D352 of beta-subunit, zinc-bound D297 of beta-subunit, two water molecules, and one oxygen atom from the alpha- and beta-phosphates of farnesyl diphosphate. The second binding motif, WT2, is identical with the exception of the zinc-bound D297 of beta-subunit being replaced by a water molecule in the Mg2+ coordination complex. In both motifs, a key hydrogen bond between a magnesium bound water and Cys1p bridges the two metallic binding sites, and thereby reduces the equilibrium distance between the reacting atoms of farnesyl diphosphate and protein-cysteine Cys1p. The free energy profiles calculated for these systems demonstrate that the two reactive atoms approach each other more readily in the presence of Mg2+. The flexible WT2 model has the lowest barrier towards the conformational change, suggesting it is the prefered Mg2+ binding motif
Zn2+
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a single zinc ion bound to the beta subunit, near the subunit interface, which marks the location of the active site
Zn2+
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contains one Zn2+ ion per dimer, required for catalysis and peptide binding
Zn2+
zinc ion is coordinated by three residues in the beta subunit: Asp-297, Cys-299, and H-362 and a water molecule
Zn2+
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zinc ion is coordinated by three residues in the beta subunit: Asp-297, Cys-299, and H-362 and a water molecule
Zn2+
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zinc plays a major catalytic role in the mechanism of enzyme, zinc seems to activate the cysteine thiol of protein substrate for attack at C-1 of the isoprenoid substrate
Zn2+
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the zinc ion activates the cysteine thiolate for nucleophilic attack on the C1 atom of the farnesyl diphosphate substrate
Zn2+
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there is no significant change in Zn-ligand distances when a substrate binds, demonstrating that the Zn remains four-coordinate. Structural characterization of the zinc site
Zn2+
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FTase is a zinc metalloenzyme with a Zn2+ ion ligated to a histidine, cysteine and aspartate
Zn2+
required, binding and coordination structure, coordinated by residues Aspbeta297, Cysbeta299 and Hisbeta362 in FTase , overview
Zn2+
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zinc ion is coordinated by three residues in the beta subunit: Asp-297, Cys-299, and H-362 and a water molecule
Zn2+
zinc ion is coordinated by three residues in the beta subunit: Asp-297, Cys-299, and H-362 and a water molecule
additional information
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a metal-assisted nucleophile is involved in the catalytic mechanism of enzyme
additional information
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a metal-assisted nucleophile is involved in the catalytic mechanism of enzyme