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Literature summary extracted from

  • Park, H.W.; Beese, L.S.
    Protein farnesyltransferase (1997), Curr. Opin. Struct. Biol., 7, 873-880.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.5.1.58 medicine evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers Homo sapiens
2.5.1.58 medicine evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers Rattus norvegicus
2.5.1.58 medicine evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers Saccharomyces cerevisiae
2.5.1.58 medicine prime target for development of anticancer therapeutics Homo sapiens
2.5.1.58 medicine prime target for development of anticancer therapeutics Rattus norvegicus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.5.1.58
-
 Rattus norvegicus

Protein Variants

EC Number Protein Variants Comment Organism
2.5.1.58 C309A lower kcat than the wild-type enzyme Saccharomyces cerevisiae
2.5.1.58 D109N loss of affinity of the enzyme for its protein substrate Saccharomyces cerevisiae
2.5.1.58 D200N decrease of protein substrate affinity without affecting the affinity for farnesyl diphosphate substrates Homo sapiens
2.5.1.58 D307A lower kcat than the wild-type enzyme Saccharomyces cerevisiae
2.5.1.58 E256A 130fold higher Km for the farnesyl diphosphate substrate Saccharomyces cerevisiae
2.5.1.58 G249V decrease in the affinity of both protein and farnesyl diphosphate substrates Homo sapiens
2.5.1.58 G259V loss of affinity of the enzyme for its protein substrate Saccharomyces cerevisiae
2.5.1.58 G328S loss of affinity of the enzyme for its protein substrate Saccharomyces cerevisiae
2.5.1.58 G349S decrease of protein substrate affinity without affecting the affinity for farnesyl diphosphate substrates Homo sapiens
2.5.1.58 H363A lower kcat than the wild-type enzyme Saccharomyces cerevisiae
2.5.1.58 K164N mutation abolishes enzyme activity Rattus norvegicus
2.5.1.58 additional information
-
 Rattus norvegicus
2.5.1.58 additional information H248beta, R291beta, K294beta, W303beta involved with the binding and utilization of the farnesyl diphophate substrate, mutations in R202beta affect the binding of the protein substrate Homo sapiens
2.5.1.58 N199D mutation reduces enzyme activity Rattus norvegicus
2.5.1.58 R172E mutation reduces enzyme activity Rattus norvegicus
2.5.1.58 R211Q lower kcat than the wild-type enzyme Saccharomyces cerevisiae
2.5.1.58 W203H mutation reduces enzyme activity Rattus norvegicus
2.5.1.58 Y166F mutation reduces enzyme activity Rattus norvegicus
2.5.1.58 Y310F lower kcat than the wild-type enzyme Saccharomyces cerevisiae

General Stability

EC Number General Stability Organism
2.5.1.58 the heterodimer cannot be dissociated unless it is denaturated, and each individual subunit appears to be unstable in solution, the number of hydrogen bonds found in the enzyme subunit interface may explain the unusual stability of the heterodimer Rattus norvegicus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.5.1.58 Co2+ evidence for a catalytically relevant interaction between the metal ion and the protein substrate in the enzyme Rattus norvegicus
2.5.1.58 Zn2+ required Rattus norvegicus
2.5.1.58 Zn2+ required Saccharomyces cerevisiae
2.5.1.58 Zn2+ zinc ion is coordinated by three residues in the beta subunit: Asp-297, Cys-299, and H-362 and a water molecule Rattus norvegicus
2.5.1.58 Zn2+ a single zinc ion bound to the beta subunit, near the subunit interface, which marks the location of the active site Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.5.1.58 46000
-
 alpha,beta, 1 * 48000 + 1 * 46000 Rattus norvegicus
2.5.1.58 46000
-
 alpha,beta, 1 * 48000 + 1 * 46000 Saccharomyces cerevisiae
2.5.1.58 48000
-
 alpha,beta, 1 * 48000 + 1 * 46000 Rattus norvegicus
2.5.1.58 48000
-
 alpha,beta, 1 * 48000 + 1 * 46000 Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.58 farnesyl diphosphate + protein-cysteine Homo sapiens process required for the transforming activity of oncogenic variants of Ras, making enzyme a prime target for anticancer therapeutics S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine Rattus norvegicus process required for the transforming activity of oncogenic variants of Ras, making enzyme a prime target for anticancer therapeutics S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine Saccharomyces cerevisiae process required for the transforming activity of oncogenic variants of Ras, making enzyme a prime target for anticancer therapeutics S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine Homo sapiens process necessary for the subcellular localisation of substrate to the plasma membrane S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine Rattus norvegicus process necessary for the subcellular localisation of substrate to the plasma membrane S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine Saccharomyces cerevisiae process necessary for the subcellular localisation of substrate to the plasma membrane S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine Rattus norvegicus enzyme responsible for catalysing isoprene lipid modifications S-farnesyl protein + diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.58 Homo sapiens
-
-
-
2.5.1.58 Rattus norvegicus
-
-
-
2.5.1.58 Saccharomyces cerevisiae
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.5.1.58 farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate farnesyl diphosphate binds exclusively to the beta subunit Rattus norvegicus
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.58 farnesyl diphosphate + protein-cysteine
-
 Homo sapiens diphosphate + S-farnesyl protein
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine
-
 Saccharomyces cerevisiae diphosphate + S-farnesyl protein
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine posttranslational lipid modification in which a 15-carbon farnesyl isoprenoid is linked via a thioether bond to specific cysteine residues of proteins, the reactive cysteine is located in the C-terminal Ca1a2X motif in which C is the modified cysteine, a1 and a2 are often an aliphatic residue, and X is Ser, Met, Ala or Gln Rattus norvegicus diphosphate + S-farnesyl protein
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine process required for the transforming activity of oncogenic variants of Ras, making enzyme a prime target for anticancer therapeutics Homo sapiens S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine process required for the transforming activity of oncogenic variants of Ras, making enzyme a prime target for anticancer therapeutics Rattus norvegicus S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine process required for the transforming activity of oncogenic variants of Ras, making enzyme a prime target for anticancer therapeutics Saccharomyces cerevisiae S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine process necessary for the subcellular localisation of substrate to the plasma membrane Homo sapiens S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine process necessary for the subcellular localisation of substrate to the plasma membrane Rattus norvegicus S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine process necessary for the subcellular localisation of substrate to the plasma membrane Saccharomyces cerevisiae S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 farnesyl diphosphate + protein-cysteine enzyme responsible for catalysing isoprene lipid modifications Rattus norvegicus S-farnesyl protein + diphosphate
-
 ?
2.5.1.58 additional information although farnesyl diphosphate and geranylgeranyl diphosphate bind competitively, the geranyl geranyl diphosphate is not transferred efficiently to the protein substrate by enzyme Rattus norvegicus ?
-
 ?
2.5.1.58 additional information not: geranylgeranyl diphosphate Rattus norvegicus ?
-
 ?

Subunits

EC Number Subunits Comment Organism
2.5.1.58 heterodimer
-
 Homo sapiens
2.5.1.58 heterodimer alpha,beta, 1 * 48000 + 1 * 46000 Rattus norvegicus
2.5.1.58 heterodimer alpha,beta, 1 * 48000 + 1 * 46000 Saccharomyces cerevisiae
2.5.1.58 More the secondary structures of alpha subunit include 15 alpha helices, three short 3,10 helices and a beta strand, the beta subunit contains 14 alpha helices, seven short 3,10 helices and three beta strands Rattus norvegicus