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Literature summary for 2.5.1.58 extracted from
- Protein farnesyltransferase (1997), Curr. Opin. Struct. Biol., 7, 873-880.
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers | Homo sapiens |
| medicine | evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers | Rattus norvegicus |
| medicine | evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers | Saccharomyces cerevisiae |
| medicine | prime target for development of anticancer therapeutics | Homo sapiens |
| medicine | prime target for development of anticancer therapeutics | Rattus norvegicus |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
- |
Rattus norvegicus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| C309A | lower kcat than the wild-type enzyme | Saccharomyces cerevisiae |
| D109N | loss of affinity of the enzyme for its protein substrate | Saccharomyces cerevisiae |
| D200N | decrease of protein substrate affinity without affecting the affinity for farnesyl diphosphate substrates | Homo sapiens |
| D307A | lower kcat than the wild-type enzyme | Saccharomyces cerevisiae |
| E256A | 130fold higher Km for the farnesyl diphosphate substrate | Saccharomyces cerevisiae |
| G249V | decrease in the affinity of both protein and farnesyl diphosphate substrates | Homo sapiens |
| G259V | loss of affinity of the enzyme for its protein substrate | Saccharomyces cerevisiae |
| G328S | loss of affinity of the enzyme for its protein substrate | Saccharomyces cerevisiae |
| G349S | decrease of protein substrate affinity without affecting the affinity for farnesyl diphosphate substrates | Homo sapiens |
| H363A | lower kcat than the wild-type enzyme | Saccharomyces cerevisiae |
| K164N | mutation abolishes enzyme activity | Rattus norvegicus |
| additional information | - |
Rattus norvegicus |
| 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 |
| N199D | mutation reduces enzyme activity | Rattus norvegicus |
| R172E | mutation reduces enzyme activity | Rattus norvegicus |
| R211Q | lower kcat than the wild-type enzyme | Saccharomyces cerevisiae |
| W203H | mutation reduces enzyme activity | Rattus norvegicus |
| Y166F | mutation reduces enzyme activity | Rattus norvegicus |
| Y310F | lower kcat than the wild-type enzyme | Saccharomyces cerevisiae |
General Stability
| General Stability | Organism |
|---|---|
| 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
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Co2+ | evidence for a catalytically relevant interaction between the metal ion and the protein substrate in the enzyme | Rattus norvegicus |  |
| Zn2+ | required | Rattus norvegicus | |
| Zn2+ | required | Saccharomyces cerevisiae | |
| 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 | |
| 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]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 46000 | - |
alpha,beta, 1 * 48000 + 1 * 46000 | Rattus norvegicus |
| 46000 | - |
alpha,beta, 1 * 48000 + 1 * 46000 | Saccharomyces cerevisiae |
| 48000 | - |
alpha,beta, 1 * 48000 + 1 * 46000 | Rattus norvegicus |
| 48000 | - |
alpha,beta, 1 * 48000 + 1 * 46000 | Saccharomyces cerevisiae |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | - |
? | |
| 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 | - |
? | |
| 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 | - |
? | |
| farnesyl diphosphate + protein-cysteine | Homo sapiens | process necessary for the subcellular localisation of substrate to the plasma membrane | S-farnesyl protein + diphosphate | - |
? | |
| farnesyl diphosphate + protein-cysteine | Rattus norvegicus | process necessary for the subcellular localisation of substrate to the plasma membrane | S-farnesyl protein + diphosphate | - |
? | |
| farnesyl diphosphate + protein-cysteine | Saccharomyces cerevisiae | process necessary for the subcellular localisation of substrate to the plasma membrane | S-farnesyl protein + diphosphate | - |
? | |
| farnesyl diphosphate + protein-cysteine | Rattus norvegicus | enzyme responsible for catalysing isoprene lipid modifications | S-farnesyl protein + diphosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
| Saccharomyces cerevisiae | - |
- |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate | farnesyl diphosphate binds exclusively to the beta subunit | Rattus norvegicus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| farnesyl diphosphate + protein-cysteine | - |
Homo sapiens | diphosphate + S-farnesyl protein | - |
? | |
| farnesyl diphosphate + protein-cysteine | - |
Saccharomyces cerevisiae | diphosphate + S-farnesyl protein | - |
? | |
| 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 | - |
? | |
| 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 | - |
? | |
| 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 | - |
? | |
| 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 | - |
? | |
| farnesyl diphosphate + protein-cysteine | process necessary for the subcellular localisation of substrate to the plasma membrane | Homo sapiens | S-farnesyl protein + diphosphate | - |
? | |
| farnesyl diphosphate + protein-cysteine | process necessary for the subcellular localisation of substrate to the plasma membrane | Rattus norvegicus | S-farnesyl protein + diphosphate | - |
? | |
| farnesyl diphosphate + protein-cysteine | process necessary for the subcellular localisation of substrate to the plasma membrane | Saccharomyces cerevisiae | S-farnesyl protein + diphosphate | - |
? | |
| farnesyl diphosphate + protein-cysteine | enzyme responsible for catalysing isoprene lipid modifications | Rattus norvegicus | S-farnesyl protein + diphosphate | - |
? | |
| 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 | ? | - |
? | |
| additional information | not: geranylgeranyl diphosphate | Rattus norvegicus | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterodimer | - |
Homo sapiens |
| heterodimer | alpha,beta, 1 * 48000 + 1 * 46000 | Rattus norvegicus |
| heterodimer | alpha,beta, 1 * 48000 + 1 * 46000 | Saccharomyces cerevisiae |
| 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 |
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