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Literature summary extracted from

  • Shen, M.; Pan, P.; Li, Y.; Li, D.; Yu, H.; Hou, T.
    Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling (2015), Drug Discov. Today, 20, 267-276.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.5.1.58 pharmacology the enzyme is a promising therapeutic target for the treatment of various Ras-induced cancers and several other kinds of diseases Homo sapiens
2.5.1.59 pharmacology the enzyme is a promising therapeutic target for the treatment of various Ras-induced cancers and several other kinds of diseases Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.58 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile binds into the CAAX peptide site and competes with the CAAX substrate of FTase; binds into the CAAX peptide site and competes with the CAAX substrate of FTase Homo sapiens
2.5.1.58 BMS-214662 bind into the CAAX peptide site and compete with the CAAX substrate of FTase; bind into the CAAX peptide site and compete with the CAAX substrate of FTase Homo sapiens
2.5.1.58 lonafarnib active in Ras-dependent and -independent malignant tumors; active in Ras-dependent and -independent malignant tumors Homo sapiens
2.5.1.58 methyl (2S)-2-([(2S)-2-[(2-[[(2R)-2-amino-3-sulfanylpropyl]amino]-3-methylpentyl)oxy]-3-phenylpropanoyl]amino)-4-(methylsulfonyl)butanoate a selective peptidomimetic enzme inhibitor Homo sapiens
2.5.1.58 additional information inhibition mechanisms for FTase and GGTase-I, EC 2.5.1.59, are different. Two classes of FTase enzyme inhibitors, bisubstrate imidazole-containing derivatives linked by an acidic substituent and a peptidyl chain and peptidomimetic molecules, which can be divided into two groups, namely thiol and non-thiol compounds. Molecular modeling studies of FTase and protein-inhibitor interactions, overview; inhibition mechanisms for FTase and GGTase-I, EC 2.5.1.59, are different. Two classes of FTase enzyme inhibitors, bisubstrate imidazole-containing derivatives linked by an acidic substituent and a peptidyl chain and peptidomimetic molecules, which can be divided into two groups, namely thiol and non-thiol compounds. Molecular modeling studies of FTase and protein-inhibitor interactions, overview Homo sapiens
2.5.1.58 R115777
-
 Homo sapiens
2.5.1.58 tipifarnib
-
 Homo sapiens
2.5.1.59 (2R,3R,5S)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid compete with the substrate protein rather than GGPP; compete with the substrate protein rather than GGPP Homo sapiens
2.5.1.59 2-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid compete with the substrate protein rather than GGPP; compete with the substrate protein rather than GGPP Homo sapiens
2.5.1.59 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile is bound to the peptide-binding site by competing with the CAAX substrate in the 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile-FTase complex, cf. EC 2.5.1.58, but is bound in the lipid-binding pocket together with a portion of the peptide-binding site in the 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile-GGTase-I complex; is bound to the peptide-binding site by competing with the CAAX substrate in the 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile–FTase complex, cf. EC 2.5.1.58, but is bound in the lipid-binding pocket together with a portion of the peptide-binding site in the L-4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile-GGTase-I complex Homo sapiens
2.5.1.59 methyl N-([2-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridin-3-yl]carbonyl)leucinate with anti-tumor activity; with anti-tumor activity Homo sapiens
2.5.1.59 additional information most GGT inhibitors are CAAX-competitive inhibitors, except for a few GGPP-competitive inhibitors. Inhibition mechanisms for FTase, EC 2.5.1.58, and GGTase-I are different. Molecular modeling studies of GGTase-I and protein-inhibitor interactions, overview; most GGT inhibitors are CAAX-competitive inhibitors, except for a few GGPP-competitive inhibitors. Inhibition mechanisms for FTase, EC 2.5.1.58, and GGTase-I are different. Molecular modeling studies of GGTase-I and protein-inhibitor interactions, overview Homo sapiens
2.5.1.59 additional information most GGT inhibitors are CAAX-competitive inhibitors, except for a few GGPP-competitive inhibitors; most GGT inhibitors are CAAX-competitive inhibitors, except for a few GGPP-competitive inhibitors Rattus norvegicus
2.5.1.59 N-([(2S)-2-benzyl-4-[(4-methyl-1H-imidazol-5-yl)methyl]-3-oxopiperazin-1-yl]carbonyl)-L-leucine
-
 Homo sapiens
2.5.1.59 N-([5-[(1H-imidazol-5-ylamino)methyl]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine a non-thiol-containing peptidomi-metic, it can inhibit human tumor growth in mice and the combination therapy with cytotoxic agents is more beneficial than monotherapy. N-([5-[(1H-imidazol-5-ylamino)methyl]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine is able to induce breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice; a non-thiol-containing peptidomi-metic, it can inhibit human tumor growth in mice and the combination therapy with cytotoxic agents is more beneficial than monotherapy. N-([5-[(1H-imidazol-5-ylamino)methyl]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine is able to induce breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice Homo sapiens
2.5.1.59 N-[(5-[[(2R)-2-amino-3-sulfanylpropyl]amino]biphenyl-2-yl)carbonyl]-L-leucine
-
 Homo sapiens
2.5.1.59 N-[[4-(imidazol-4-yl)methylamino]-2-(1-naphthyl)benzoyl]leucine
-
 Homo sapiens
2.5.1.59 Na-(4-[[1-(3,4-dichlorophenyl)-4-[2-(methylsulfanyl)ethyl]-3-(pyridin-3-yl)-1H-pyrazol-5-yl]oxy]butanoyl)-L-phenylalaninamide
-
 Homo sapiens
2.5.1.59 Na-([(5R)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrol-3-yl]carbonyl)-L-phenylalaninamide with anti-tumor activity; with anti-tumor activity Homo sapiens
2.5.1.59 tetrapeptide CVIL superposition of the crystal structures of the CVIL-GGTase-I complex; superposition of the crystal structures of the CVIL-GGTase-I complex Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.5.1.58 Mg2+ required Homo sapiens
2.5.1.58 Zn2+ required Homo sapiens
2.5.1.58 Zn2+ required, binding and coordination structure, coordinated by residues Aspbeta297, Cysbeta299 and Hisbeta362 in FTase , overview Rattus norvegicus
2.5.1.58 Zn2+ required, binding and coordination structure, overview Rattus norvegicus
2.5.1.59 additional information Mg2+ is not required Rattus norvegicus
2.5.1.59 additional information Mg2+ is not required Homo sapiens
2.5.1.59 Zn2+ required for the enzymatic activities of GGTase-I, bound at the beta-subunit Homo sapiens
2.5.1.59 Zn2+ required for the enzymatic activities of GGTase-I, bound at the beta-subunit, coordinated by residues Aspbeta269, Cysbeta271 and Hisbeta321 in GGTase-I Rattus norvegicus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.5.1.59 48000
-
-
 Rattus norvegicus
2.5.1.59 48000
-
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.58 (2E,6E)-farnesyl diphosphate + (protein)-L-cysteine Homo sapiens
-
 S-(2E,6E)-farnesyl protein + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [H Ras]-L-cysteine Rattus norvegicus
-
 S-(2E,6E)-farnesyl-[H Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [H Ras]-L-cysteine Homo sapiens
-
 S-(2E,6E)-farnesyl-[H Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [K Ras]-L-cysteine Rattus norvegicus
-
 S-(2E,6E)-farnesyl-[K Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [K Ras]-L-cysteine Homo sapiens
-
 S-(2E,6E)-farnesyl-[K Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [N Ras]-L-cysteine Rattus norvegicus
-
 S-(2E,6E)-farnesyl-[N Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [N Ras]-L-cysteine Homo sapiens
-
 S-(2E,6E)-farnesyl-[N Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine Rattus norvegicus
-
 S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine Homo sapiens
-
 S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [Rho]-L-cysteine Rattus norvegicus
-
 S-(2E,6E)-farnesyl-[Rho]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [Rho]-L-cysteine Homo sapiens
-
 S-(2E,6E)-farnesyl-[Rho]-L-cysteine + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + K Ras-cysteine Rattus norvegicus
-
 S-geranylgeranyl-K Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + K Ras-cysteine Homo sapiens
-
 S-geranylgeranyl-K Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + N-Ras-cysteine Rattus norvegicus
-
 S-geranylgeranyl-N-Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + N-Ras-cysteine Homo sapiens
-
 S-geranylgeranyl-N-Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + protein-cysteine Rattus norvegicus
-
 S-geranylgeranyl-protein + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + protein-cysteine Homo sapiens
-
 S-geranylgeranyl-protein + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rac-cysteine Rattus norvegicus
-
 S-geranylgeranyl-Rac + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rac-cysteine Homo sapiens
-
 S-geranylgeranyl-Rac + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap-cysteine Rattus norvegicus
-
 S-geranylgeranyl-Rap + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap-cysteine Homo sapiens
-
 S-geranylgeranyl-Rap + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap1A-cysteine Rattus norvegicus
-
 S-geranylgeranyl-Rap1A + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap1A-cysteine Homo sapiens
-
 S-geranylgeranyl-Rap1A + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho-cysteine Rattus norvegicus
-
 S-geranylgeranyl-Rho + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho-cysteine Homo sapiens
-
 S-geranylgeranyl-Rho + diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.58 Homo sapiens P49354 alpha-subunit
-
2.5.1.58 Homo sapiens P49356 beta-subunit
-
2.5.1.58 Rattus norvegicus Q02293 beta-subunit
-
2.5.1.58 Rattus norvegicus Q04631 alpha-subunit
-
2.5.1.59 Homo sapiens P49354 subunit alpha
-
2.5.1.59 Homo sapiens P53609 subunit beta
-
2.5.1.59 Rattus norvegicus P53610 subunit beta
-
2.5.1.59 Rattus norvegicus Q04631 subunit alpha
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.58 (2E,6E)-farnesyl diphosphate + (protein)-L-cysteine
-
 Homo sapiens S-(2E,6E)-farnesyl protein + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + K Ras-cysteine
-
 Rattus norvegicus S-(2E,6E)-farnesyl-[K Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [H Ras]-L-cysteine
-
 Rattus norvegicus S-(2E,6E)-farnesyl-[H Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [H Ras]-L-cysteine
-
 Homo sapiens S-(2E,6E)-farnesyl-[H Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [K Ras]-L-cysteine
-
 Rattus norvegicus S-(2E,6E)-farnesyl-[K Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [K Ras]-L-cysteine
-
 Homo sapiens S-(2E,6E)-farnesyl-[K Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [N Ras]-L-cysteine
-
 Rattus norvegicus S-(2E,6E)-farnesyl-[N Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [N Ras]-L-cysteine
-
 Homo sapiens S-(2E,6E)-farnesyl-[N Ras]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine
-
 Rattus norvegicus S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine
-
 Homo sapiens S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [Rho]-L-cysteine
-
 Rattus norvegicus S-(2E,6E)-farnesyl-[Rho]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [Rho]-L-cysteine
-
 Homo sapiens S-(2E,6E)-farnesyl-[Rho]-L-cysteine + diphosphate
-
 ?
2.5.1.58 additional information FTase-I can transfer isoprenoids to intracellular proteins that contain CAAX motifs. The isoprenoid groups can be selectively recognized by GGTase-I. The 15-carbon isoprenoid geranylgeranyl from its donor farnesyldiphosphate (FPP) is specific to FTase-I. Residues Lysalpha164, Hisbeta248, Argbeta291 and Tyrbeta300 in FTase can form hydrogen bonds with farnesyl diphosphate. When FTase is inhibited by a FTI, N-Ras and K-Ras can be alternatively prenylated by GGTase-I, EC 2.5.1.59, but H-Ras cannot Rattus norvegicus ?
-
 ?
2.5.1.58 additional information FTase-I can transfer isoprenoids to intracellular proteins that contain CAAX motifs. The isoprenoid groups can be selectively recognized by GGTase-I. The 15-carbon isoprenoid geranylgeranyl from its donor farnesyldiphosphate (FPP) is specific to FTase-I. Residues Lysalpha164, Hisbeta248, Argbeta291 and Tyrbeta300 in FTase can form hydrogen bonds with farnesyl diphosphate. When FTase is inhibited by a FTI, N-Ras and K-Ras can be alternatively prenylated by GGTase-I, EC 2.5.1.59, but H-Ras cannot Homo sapiens ?
-
 ?
2.5.1.59 geranylgeranyl diphosphate + K Ras-cysteine
-
 Rattus norvegicus S-geranylgeranyl-K Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + K Ras-cysteine
-
 Homo sapiens S-geranylgeranyl-K Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + N-Ras-cysteine
-
 Rattus norvegicus S-geranylgeranyl-N-Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + N-Ras-cysteine
-
 Homo sapiens S-geranylgeranyl-N-Ras + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + protein-cysteine
-
 Rattus norvegicus S-geranylgeranyl-protein + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + protein-cysteine
-
 Homo sapiens S-geranylgeranyl-protein + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rac-cysteine
-
 Rattus norvegicus S-geranylgeranyl-Rac + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rac-cysteine
-
 Homo sapiens S-geranylgeranyl-Rac + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap-cysteine
-
 Rattus norvegicus S-geranylgeranyl-Rap + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap-cysteine
-
 Homo sapiens S-geranylgeranyl-Rap + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap1A-cysteine
-
 Rattus norvegicus S-geranylgeranyl-Rap1A + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rap1A-cysteine
-
 Homo sapiens S-geranylgeranyl-Rap1A + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho-cysteine
-
 Rattus norvegicus S-geranylgeranyl-Rho + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho-cysteine
-
 Homo sapiens S-geranylgeranyl-Rho + diphosphate
-
 ?
2.5.1.59 additional information GGTase-I can transfer isoprenoids to intracellular proteins that contain CAAX motifs. The isoprenoid groups can be selectively recognized by GGTase-I. The 20-carbon isoprenoid geranylgeranyl from its donor geranylgeranyl diphosphate (GGPP) is specific to GGTase-I. No activity with H-Ras Homo sapiens ?
-
 ?
2.5.1.59 additional information GGTase-I can transfer isoprenoids to intracellular proteins that contain CAAX motifs. The isoprenoid groups can be selectively recognized by GGTase-I. The 20-carbon isoprenoid geranylgeranyl from its donor geranylgeranyl diphosphate (GGPP) is specific to GGTase-I. Residues Lysalpha164, Hisbeta219, Argbeta263, Lysbeta266 and Tyrbeta272 in GGTase-I can form hydrogen bonds with GGPP. No activity with H-Ras Rattus norvegicus ?
-
 ?

Subunits

EC Number Subunits Comment Organism
2.5.1.59 heterodimer alphabeta, 1 * 48000, alpha-subunit Rattus norvegicus
2.5.1.59 heterodimer alphabeta, 1 * 48000, alpha-subunit Homo sapiens
2.5.1.59 More the alpha subunit is primarily composed of alpha helices that are arranged into different shapes. The alpha subunit is a crescent-shaped super helix. The N-terminal domain is disordered and proline-rich, and has no direct influence on the catalytic activity Rattus norvegicus
2.5.1.59 More the alpha subunit is primarily composed of alpha helices that are arranged into different shapes. The alpha subunit is a crescent-shaped super helix. The N-terminal domain is disordered and proline-rich, and has no direct influence on the catalytic activity Homo sapiens
2.5.1.59 More the beta subunit is primarily composed of alpha helices that are arranged into different shapes. The beta subunit is an alpha-alpha barrel. The beta subunit of GGTase-I consists of 13 alpha helices, with 12 alpha helices folded into an alpha-alpha barrel. This arrangement forms a funnel-shaped cavity in the center of the barrel, where the active sites of GGTase-I is located. This cavity is hydrophobic and contains a number of conserved aromatic residues. The N-terminal domain is disordered and proline-rich, and has no direct influence on the catalytic activity Rattus norvegicus
2.5.1.59 More the beta subunit is primarily composed of alpha helices that are arranged into different shapes. The beta subunit is an alpha-alpha barrel. The beta subunit of GGTase-I consists of 13 alpha helices, with 12 alpha helices folded into an alpha-alpha barrel. This arrangement forms a funnel-shaped cavity in the center of the barrel, where the active sites of GGTase-I is located. This cavity is hydrophobic and contains a number of conserved aromatic residues. The N-terminal domain is disordered and proline-rich, and has no direct influence on the catalytic activity Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.5.1.58 farnesyltransferase
-
 Rattus norvegicus
2.5.1.58 farnesyltransferase
-
 Homo sapiens
2.5.1.58 FTase
-
 Rattus norvegicus
2.5.1.58 FTase
-
 Homo sapiens
2.5.1.59 geranylgeranyltransferase type-I
-
 Rattus norvegicus
2.5.1.59 geranylgeranyltransferase type-I
-
 Homo sapiens
2.5.1.59 GGTase-I
-
 Rattus norvegicus
2.5.1.59 GGTase-I
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.5.1.59 0.0000008
-
 Na-(4-[[1-(3,4-dichlorophenyl)-4-[2-(methylsulfanyl)ethyl]-3-(pyridin-3-yl)-1H-pyrazol-5-yl]oxy]butanoyl)-L-phenylalaninamide pH and temperature not specified in the publication Homo sapiens
2.5.1.59 0.0000095
-
 N-([(2S)-2-benzyl-4-[(4-methyl-1H-imidazol-5-yl)methyl]-3-oxopiperazin-1-yl]carbonyl)-L-leucine pH and temperature not specified in the publication Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.5.1.58 0.00024
-
 pH and temperature not specified in the publication Homo sapiens methyl (2S)-2-([(2S)-2-[(2-[[(2R)-2-amino-3-sulfanylpropyl]amino]-3-methylpentyl)oxy]-3-phenylpropanoyl]amino)-4-(methylsulfonyl)butanoate
2.5.1.59 0.000313
-
 pH and temperature not specified in the publication Homo sapiens Na-(4-[[1-(3,4-dichlorophenyl)-4-[2-(methylsulfanyl)ethyl]-3-(pyridin-3-yl)-1H-pyrazol-5-yl]oxy]butanoyl)-L-phenylalaninamide
2.5.1.59 0.000466
-
 pH and temperature not specified in the publication Homo sapiens N-([(2S)-2-benzyl-4-[(4-methyl-1H-imidazol-5-yl)methyl]-3-oxopiperazin-1-yl]carbonyl)-L-leucine

General Information

EC Number General Information Comment Organism
2.5.1.58 malfunction combined FTase/GGTase-I deficiency significantly reduces K-Ras-induced lung tumors and improves survival without obvious pulmonary toxicity Rattus norvegicus
2.5.1.58 malfunction combined FTase/GGTase-I deficiency significantly reduces K-Ras-induced lung tumors and improves survival without obvious pulmonary toxicity. Enzyme deficiency is involved in progeria, also known as Hutchinson-Gilford progeria syndrome, a fatal and rare genetic disease caused by the mutation of the LMNA gene Homo sapiens
2.5.1.58 additional information FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I Rattus norvegicus
2.5.1.58 additional information FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I Homo sapiens
2.5.1.58 physiological function FTase catalyzes farnesyl isoprenoid linked to the cysteine residue of the CAAX protein through a thioether linkage, which will enhance the hydrophobicity of the CAAX protein. Meanwhile, the formed CAAX-protein-isoprenoid complex is attached to the endoplasmic reticulum surface Rattus norvegicus
2.5.1.58 physiological function FTase catalyzes farnesyl isoprenoid linked to the cysteine residue of the CAAX protein through a thioether linkage, which will enhance the hydrophobicity of the CAAX protein. Meanwhile, the formed CAAX-protein-isoprenoid complex is attached to the endoplasmic reticulum surface. FTase is involvedin hematologic malignancies due via prenylation of Ras. The enzyme is also important in the pathological process of neurological diseases, such as neuroinflammatory disease and Parkinson's disease Homo sapiens
2.5.1.59 malfunction combined FTase/GGTase-I deficiency significantly reduces K-Ras-induced lung tumors and improves survival without obvious pulmonary toxicity Rattus norvegicus
2.5.1.59 malfunction combined FTase/GGTase-I deficiency significantly reduces K-Ras-induced lung tumors and improves survival without obvious pulmonary toxicity Homo sapiens
2.5.1.59 additional information FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I Rattus norvegicus
2.5.1.59 additional information FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I Homo sapiens
2.5.1.59 physiological function enzyme GGTase-I has a crucial role in the posttranslational modification of Ras proteins. The enzyme is involved in several diseases, e.g. glaucoma via Rho prenylation, and neurological diseases. GGTase-I catalyzes geranylgeranyl isoprenoid linked to the cysteine residue of the CAAX protein through a thioether linkage, which will enhance the hydrophobicity of the CAAX protein. Meanwhile, the formed CAAX-protein-isoprenoid complex is attached to the endoplasmic reticulum surface Rattus norvegicus
2.5.1.59 physiological function enzyme GGTase-I has a crucial role in the posttranslational modification of Ras proteins. The enzyme is involved in several diseases, e.g. glaucoma via Rho prenylation, and neurological diseases. GGTase-I catalyzes geranylgeranyl isoprenoid linked to the cysteine residue of the CAAX protein through a thioether linkage, which will enhance the hydrophobicity of the CAAX protein. Meanwhile, the formed CAAX-protein-isoprenoid complex is attached to the endoplasmic reticulum surface Homo sapiens