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Information on EC 2.5.1.59 - protein geranylgeranyltransferase type I and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
This enzyme, along with protein farnesyltransferase (EC 2.5.1.58) and protein geranylgeranyltransferase type II (EC 2.5.1.60), constitutes the protein prenyltransferase family of enzymes. Catalyses the formation of a thioether linkage between the C-1 atom of the geranylgeranyl group and a cysteine residue fourth from the C-terminus of the protein. These protein acceptors have the C-terminal sequence CA1A2X, where the terminal residue, X, is preferably leucine; serine, methionine, alanine or glutamine makes the protein a substrate for EC 2.5.1.58. The enzymes are relaxed in specificity for A1, but cannot act if A2 is aromatic. Known targets of this enzyme include most gamma-subunits of heterotrimeric G proteins and Ras-related GTPases such as members of the Ras and Rac/Rho families. A zinc metalloenzyme. The Zn2+ is required for peptide, but not for isoprenoid, substrate binding.
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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
ggtase-i, ggtase i, ggtase, geranylgeranyltransferase i, pggt-i, cdc43, protein geranylgeranyltransferase type i, geranylgeranyltransferase type i, protein geranylgeranyltransferase, geranylgeranyltransferase-i, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CAAX geranylgeranyltransferase
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geranylgeranyl protein transferase type I
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geranylgeranyltransferase I
geranylgeranyltransferase type-I
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geranylgeranyltransferase-1
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geranylgeranyltransferase-I
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geranylgeranyltransferaseI
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GGT I
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GGTase I
GGTase-I
GGTaseI
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PGGT
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PGGT-I
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PGGTase-I
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PGGTaseI
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protein geranylgeranyltransferase
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protein geranylgeranyltransferase I
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protein geranylgeranyltransferase type I
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protein geranylgeranyltransferase type-I
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protein geranylgeranyltransferase-I
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SYSTEMATIC NAME
IUBMB Comments
geranylgeranyl-diphosphate:protein-cysteine geranyltransferase
This enzyme, along with protein farnesyltransferase (EC 2.5.1.58) and protein geranylgeranyltransferase type II (EC 2.5.1.60), constitutes the protein prenyltransferase family of enzymes. Catalyses the formation of a thioether linkage between the C-1 atom of the geranylgeranyl group and a cysteine residue fourth from the C-terminus of the protein. These protein acceptors have the C-terminal sequence CA1A2X, where the terminal residue, X, is preferably leucine; serine, methionine, alanine or glutamine makes the protein a substrate for EC 2.5.1.58. The enzymes are relaxed in specificity for A1, but cannot act if A2 is aromatic. Known targets of this enzyme include most gamma-subunits of heterotrimeric G proteins and Ras-related GTPases such as members of the Ras and Rac/Rho families. A zinc metalloenzyme. The Zn2+ is required for peptide, but not for isoprenoid, substrate binding.
CAS REGISTRY NUMBER
COMMENTARY hide
135371-29-8
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]-oxadiazo-4-ylamino)-dodeca-2,6,10-trien-1-diphosphate + GST-RhoA
diphosphate + ?
show the reaction diagram
-
-
-
-
?
3,7-dimethyl-8-(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-octa-2,6-diene-1-diphosphate + GST-RhoA
diphosphate + ?
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + Ki-Ras4B
diphosphate + S-geranylgeranyl-Ki-Ras4B
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + protein-cysteine
S-farnesyl protein + diphosphate
show the reaction diagram
geranylgeranyl diphosphate + Asp-Asp-Pro-Thr-Ala-Ser-Ala-Cys-Val-Leu-Leu
Asp-Asp-Pro-Thr-Ala-Ser-Ala-(S-geranylgeranyl)-Cys-Val-Leu-Leu + diphosphate
show the reaction diagram
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-
-
-
?
geranylgeranyl diphosphate + GST-RhoA
diphosphate + GST-S-geranylgeranyl-RhoA
show the reaction diagram
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-
-
-
?
geranylgeranyl diphosphate + H-Ras-CVLL
S-geranylgeranyl-protein + ?
show the reaction diagram
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-
-
-
?
geranylgeranyl diphosphate + K Ras-cysteine
S-geranylgeranyl-K Ras + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + Ki-Ras4A
diphosphate + S-geranylgeranyl-Ki-Ras4A
show the reaction diagram
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-
-
-
?
geranylgeranyl diphosphate + Ki-Ras4B
diphosphate + S-geranylgeranyl-Ki-Ras4B
show the reaction diagram
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-
-
-
?
geranylgeranyl diphosphate + N-Ras
diphosphate + S-geranylgeranyl-N-Ras
show the reaction diagram
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-
-
-
?
geranylgeranyl diphosphate + N-Ras-cysteine
S-geranylgeranyl-N-Ras + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl protein + diphosphate
show the reaction diagram
-
the enzyme catalyzes posttranslational modification of proteins, the farnesyl moieties attached to the substrates are direcly involved in protein-protein interactions as well as in protein-membrane interactions
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-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
geranylgeranyl diphosphate + Rac-cysteine
S-geranylgeranyl-Rac + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + Rap-cysteine
S-geranylgeranyl-Rap + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + Rap1A-cysteine
S-geranylgeranyl-Rap1A + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + Ras protein
S-geranylgeranyl-Ras protein + diphosphate
show the reaction diagram
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-
?
geranylgeranyl diphosphate + Ras-Cys-Val-Leu-Leu
diphosphate + Ras-S-geranylgeranyl-Cys-Val-Leu-Leu
show the reaction diagram
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-
?
geranylgeranyl diphosphate + Rho-cysteine
S-geranylgeranyl-Rho + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + RhoA
diphosphate + S-geranylgeranyl-RhoA
show the reaction diagram
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-
?
geranylgeranyl diphosphate + rhoC protein
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
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?
geranylgeranyl diphosphate + S-geranylgeranyl-Ki-Ras4B
diphosphate + S-geranylgeranyl-Ki-Ras4B
show the reaction diagram
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both the polylysine and the carboxy-terminal methionine are important for geranylgeranylation of this substrate
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-
?
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
farnesyl diphosphate + protein-cysteine
S-farnesyl protein + diphosphate
show the reaction diagram
-
the enzyme catalyzes postttranslational modification of proteins, the farnesyl moieties attached to the substrates are direcly involved in protein-protein interactions as well as in protein-membrane interactions
-
-
?
geranylgeranyl diphosphate + K Ras-cysteine
S-geranylgeranyl-K Ras + diphosphate
show the reaction diagram
-
-
-
?
geranylgeranyl diphosphate + N-Ras-cysteine
S-geranylgeranyl-N-Ras + diphosphate
show the reaction diagram
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl protein + diphosphate
show the reaction diagram
-
the enzyme catalyzes posttranslational modification of proteins, the farnesyl moieties attached to the substrates are direcly involved in protein-protein interactions as well as in protein-membrane interactions
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
geranylgeranyl diphosphate + Rac-cysteine
S-geranylgeranyl-Rac + diphosphate
show the reaction diagram
-
-
-
?
geranylgeranyl diphosphate + Rap-cysteine
S-geranylgeranyl-Rap + diphosphate
show the reaction diagram
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-
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?
geranylgeranyl diphosphate + Rap1A-cysteine
S-geranylgeranyl-Rap1A + diphosphate
show the reaction diagram
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-
-
?
geranylgeranyl diphosphate + Ras protein
S-geranylgeranyl-Ras protein + diphosphate
show the reaction diagram
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-
-
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?
geranylgeranyl diphosphate + Rho-cysteine
S-geranylgeranyl-Rho + diphosphate
show the reaction diagram
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-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
required for the enzymatic activities of GGTase-I, bound at the beta-subunit
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(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
(2S,5R)-5-ethyl-2-(4-fluorophenyl)-1-tosyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid
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IC50: 0.2 mM using RhoA as a substrate, IC50: 0.25 mM using Ki-Ras4B as a substrate
(2S,5S)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylic acid
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IC50: 0.0005 mM using RhoA as a substrate, IC50: 0.0009 mM using Ki-Ras4B as a substrate
(2S,6S)-2,6-bis(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid
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IC50: 0.0003 mM using RhoA as a substrate, IC50: 0.002 mM using Ki-Ras4B as a substrate
(2S,6S)-6-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid
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IC50: 0.12 mM using RhoA as a substrate, IC50: 0.08 mM using Ki-Ras4B as a substrate
(S)-N-(1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide
potent GGT1 inhibitor, anti-proliferative efficacy against MDA-MB-231 cells has an IC50 value of 0.0076 mM
(S)-N-(1-amino-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide
potent GGT1 inhibitor
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid
-
IC50: 6525 nM
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid methyl ester
-
IC50: above 0.01 mM
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
2-aryl-4-aminobenzoic acid
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IC50: 21 nM
2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-N-(3-methyl-butyl)-acetamide
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IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl] acetylamino}-4-methyl-pentanoic acid methyl ester
-
IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid
-
IC50: 0.0063 mM; IC50: 170 nM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid methyl ester
-
IC50: 4500 nM; IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid
-
IC50: 2700 nM; IC50: 580 nM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid methyl ester
-
IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methylsulfanyl-butyric acid
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IC50: 3350 nM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methylsulfanyl-butyric acid methyl ester
-
IC50: above 0.01 mM
3-(4'-farnesyloxy-3'-methoxyphenyl)-2-trans propenoic acid
-
0.1 mM, 83.9% inhibition
3-(4'-farnesyloxy-3'-OH-phenyl)-2-trans propenoic acid
-
0.1 mM, 93.5% inhibition
3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid
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0.1 mM, 78.6% inhibition
3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid ethyl ester
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0.1 mM, 3% inhibition
3-(4'-geranyloxy-3'-OH-phenyl)-2-trans propenoic acid
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0.1 mM, 72.4% inhibition
3-(4'-geranyloxy-3'-OH-phenyl)-2-trans propenoic acid ethyl ester
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0.1 mM, 7.5% inhibition
3-(4'-isopentenyloxy-3'-OH-phenyl)-2-trans propenoic acid
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0.1 mM, 46.4% inhibition
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
auraptene
-
0.1 mM, 18.6% inhibition
boropinic acid
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0.1 mM, 31% inhibition
collinin
-
0.1 mM, 34.2% inhibition
GGTi-2147
specific GGTIbeta enzyme inhibitor; specific GGTIbeta enzyme inhibitor
GGTI-2418
a GGTI inhibitor, in clinical trials as potential anti-tumor agent in breast cancer; a GGTI inhibitor, in clinical trials as potential anti-tumor agent in breast cancer
GGTI-298
GGTI-DU40
L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
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
N-(12-ammoniododecanoyl)-D-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
-
-
N-(12-[[(3-[[(3R)-3-ammonio-4-phenylbutyl]oxy]-4,5-bis[[(3S)-3-ammonio-4-phenylbutyl]oxy]phenyl)carbonyl]amino]dodecanoyl)-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
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N-(4-[[(3-[[(3R)-3-ammonio-4-phenylbutyl]oxy]-4,5-bis[[(3S)-3-ammonio-4-phenylbutyl]oxy]phenyl)carbonyl]amino]butanoyl)-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
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N-([(2S)-2-benzyl-4-[(4-methyl-1H-imidazol-5-yl)methyl]-3-oxopiperazin-1-yl]carbonyl)-L-leucine
-
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
N-[(5-[[(2R)-2-amino-3-sulfanylpropyl]amino]biphenyl-2-yl)carbonyl]-L-leucine
-
N-[12-([[3,4,5-tris(3-ammoniopropoxy)phenyl]carbonyl]amino)dodecanoyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
-
-
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-hexylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
-
-
N-[[4-(imidazol-4-yl)methylamino]-2-(1-naphthyl)benzoyl]leucine
-
Na-(4-[[1-(3,4-dichlorophenyl)-4-[2-(methylsulfanyl)ethyl]-3-(pyridin-3-yl)-1H-pyrazol-5-yl]oxy]butanoyl)-L-phenylalaninamide
-
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
P61A6
derived from an allenoate-derived compound library, shows efficiency of the enzyme inhibitor to inhibit tumor growth demonstrated using human pancreatic cancer xenograft; derived from an allenoate-derived compound library, shows efficiency of the enzyme inhibitor to inhibit tumor growth demonstrated using human pancreatic cancer xenograft
tetrapeptide CVIL
superposition of the crystal structures of the CVIL-GGTase-I complex; superposition of the crystal structures of the CVIL-GGTase-I complex
umbelliprenine
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0.1 mM, 13.4% inhibition
[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetic acid benzyl ester
-
IC50: above 0.01 mM
{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-acetic acid
-
IC50: above 0.01 mM
{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-acetic acid methyl ester
-
IC50: above 0.01 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7-isopentenyloxycoumarin
-
0.1 mM, 10.3% activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00003
3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]-oxadiazo-4-ylamino)-dodeca-2,6,10-trien-1-diphosphate
-
-
0.00000133
Asp-Asp-Pro-Thr-Ala-Ser-Ala-Cys-Val-Leu-Leu
-
at 30°C
0.00003934
geranylgeranyl diphosphate
-
at 30°C
0.042
GST-RhoA
-
-
-
0.0088
Ki-Ras4A
-
pH 7.5, 37°C
-
0.012
Ki-Ras4B
-
pH 7.5, 37°C
-
0.0021
N-Ras
-
pH 7.5, 37°C
-
0.0009
Ras-Cys-Val-Leu-Leu
-
pH 7.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.08
3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]-oxadiazo-4-ylamino)-dodeca-2,6,10-trien-1-diphosphate
-
-
0.021
Asp-Asp-Pro-Thr-Ala-Ser-Ala-Cys-Val-Leu-Leu
-
at 30°C
0.021
geranylgeranyl diphosphate
-
at 30°C
0.08
GST-RhoA
-
-
-
0.0667
Ki-Ras4A
-
-
-
0.0767
Ki-Ras4B
-
-
-
0.0113
N-Ras
-
-
-
0.014
Ras-Cys-Val-Leu-Leu
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
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
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.25 - 4
(2S,5R)-5-ethyl-2-(4-fluorophenyl)-1-tosyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid
Homo sapiens
-
IC50: 0.2 mM using RhoA as a substrate, IC50: 0.25 mM using Ki-Ras4B as a substrate
0.0009 - 4
(2S,5S)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylic acid
Homo sapiens
-
IC50: 0.0005 mM using RhoA as a substrate, IC50: 0.0009 mM using Ki-Ras4B as a substrate
0.002 - 4
(2S,6S)-2,6-bis(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid
Homo sapiens
-
IC50: 0.0003 mM using RhoA as a substrate, IC50: 0.002 mM using Ki-Ras4B as a substrate
0.08 - 4
(2S,6S)-6-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid
Homo sapiens
-
IC50: 0.12 mM using RhoA as a substrate, IC50: 0.08 mM using Ki-Ras4B as a substrate
0.0024
(S)-N-(1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide
Homo sapiens
pH 7.4, 30°C
0.0031
(S)-N-(1-amino-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide
Homo sapiens
pH 7.4, 30°C
0.006525
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid
Homo sapiens
-
IC50: 6525 nM
0.01
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid methyl ester
Homo sapiens
-
IC50: above 0.01 mM
0.000021
2-aryl-4-aminobenzoic acid
Homo sapiens
-
IC50: 21 nM
0.01
2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-N-(3-methyl-butyl)-acetamide
Homo sapiens
-
IC50: above 0.01 mM
0.01
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl] acetylamino}-4-methyl-pentanoic acid methyl ester
Homo sapiens
-
IC50: above 0.01 mM
0.00017 - 0.0063
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid
0.0045 - 0.01
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid methyl ester
0.00058 - 0.0027
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid
0.01
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid methyl ester
Homo sapiens
-
IC50: above 0.01 mM
0.00335
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methylsulfanyl-butyric acid
Homo sapiens
-
IC50: 3350 nM
0.01
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methylsulfanyl-butyric acid methyl ester
Homo sapiens
-
IC50: above 0.01 mM
0.0048
L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
Homo sapiens
-
-
0.0014
N-(12-ammoniododecanoyl)-D-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
Homo sapiens
-
-
0.00098
N-(12-[[(3-[[(3R)-3-ammonio-4-phenylbutyl]oxy]-4,5-bis[[(3S)-3-ammonio-4-phenylbutyl]oxy]phenyl)carbonyl]amino]dodecanoyl)-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
Homo sapiens
-
-
0.00066
N-(4-[[(3-[[(3R)-3-ammonio-4-phenylbutyl]oxy]-4,5-bis[[(3S)-3-ammonio-4-phenylbutyl]oxy]phenyl)carbonyl]amino]butanoyl)-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
Homo sapiens
-
-
0.000466
N-([(2S)-2-benzyl-4-[(4-methyl-1H-imidazol-5-yl)methyl]-3-oxopiperazin-1-yl]carbonyl)-L-leucine
Homo sapiens
pH and temperature not specified in the publication
0.0006
N-[12-([[3,4,5-tris(3-ammoniopropoxy)phenyl]carbonyl]amino)dodecanoyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
Homo sapiens
-
-
0.000313
Na-(4-[[1-(3,4-dichlorophenyl)-4-[2-(methylsulfanyl)ethyl]-3-(pyridin-3-yl)-1H-pyrazol-5-yl]oxy]butanoyl)-L-phenylalaninamide
Homo sapiens
pH and temperature not specified in the publication
0.01
[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetic acid benzyl ester
Homo sapiens
-
IC50: above 0.01 mM
0.01
{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-acetic acid
Homo sapiens
-
IC50: above 0.01 mM
0.01
{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-acetic acid methyl ester
Homo sapiens
-
IC50: above 0.01 mM
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
high enzyme activity. GGTI expression and activity are particularly enriched in the adult brain and developmentally regulated after birth in various mammalian tissues
Manually annotated by BRENDA team
-
human trabecular meshwork cells, lysate for activity assay
Manually annotated by BRENDA team
low enzyme activity
Manually annotated by BRENDA team
-
primary culture of airway smooth muscle cell
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PGTB1_HUMAN
377
0
42368
Swiss-Prot
other Location (Reliability: 2)
FNTA_HUMAN
379
0
44409
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
alphabeta, 1 * 48000, alpha-subunit
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular docking of inhibitor (S)-N-(1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide shows several hydrogen bonding interactions and pi-pi contacts to the binding pocket of GGT1
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
nickel agarose resin chromatography
-
recombinant enzyme
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 (DE3) and Sf9 insect cells
-
PCR-amplification of human enzyme for RT-PCR analysis of expression in human trabecular mesh cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pharmacology
the enzyme is a promising therapeutic target for the treatment of various Ras-induced cancers and several other kinds of diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhang, F.L.; Kirschmeier, P.; Carr, D.; James, L.; Bond, R.W.; Wang, L.; Patton, R.; Windsor, W.T.; Syto, R.; Zhang, R.; Bishop, W.R.
Characterization of Ha-Ras, N-Ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I
J. Biol. Chem.
272
10232-10239
1997
Homo sapiens
Manually annotated by BRENDA team
Maurer-Stroh, S.; Washietl, S.; Eisenhaber, F.
Protein prenyltransferases
Genome Biol.
4
212
2003
Homo sapiens
Manually annotated by BRENDA team
Terry, K.L.; Casey, P.J.; Beese, L.S.
Conversion of protein farnesyltransferase to a geranylgeranyltransferase
Biochemistry
45
9746-9755
2006
Homo sapiens
Manually annotated by BRENDA team
Carrico, D.; Blaskovich, M.A.; Bucher, C.J.; Sebti, S.M.; Hamilton, A.D.
Design, synthesis, and evaluation of potent and selective benzoyleneurea-based inhibitors of protein geranylgeranyltransferase-I
Bioorg. Med. Chem.
13
677-688
2005
Homo sapiens
Manually annotated by BRENDA team
Epifano, F.; Curini, M.; Genovese, S.; Blaskovich, M.; Hamilton, A.; Sebti, S.M.
Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I
Bioorg. Med. Chem. Lett.
17
2639-2642
2007
Homo sapiens
Manually annotated by BRENDA team
Dursina, B.; Reents, R.; Delon, C.; Wu, Y.; Kulharia, M.; Thutewohl, M.; Veligodsky, A.; Kalinin, A.; Evstifeev, V.; Ciobanu, D.; Szedlacsek, S.E.; Waldmann, H.; Goody, R.S.; Alexandrov, K.
Identification and specificity profiling of protein prenyltransferase inhibitors using new fluorescent phosphoisoprenoids
J. Am. Chem. Soc.
128
2822-2835
2006
Homo sapiens
Manually annotated by BRENDA team
Castellano, S.; Fiji, H.D.; Kinderman, S.S.; Watanabe, M.; de Leon, P.; Tamanoi, F.; Kwon, O.
Small-molecule inhibitors of protein geranylgeranyltransferase type I
J. Am. Chem. Soc.
129
5843-5845
2007
Homo sapiens
Manually annotated by BRENDA team
Machida, S.; Usuba, K.; Blaskovich, M.A.; Yano, A.; Harada, K.; Sebti, S.M.; Kato, N.; Ohkanda, J.
Module assembly for protein-surface recognition: geranylgeranyltransferase I bivalent inhibitors for simultaneous targeting of interior and exterior protein surfaces
Chemistry
14
1392-1401
2008
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Suzuki, T.; Ito, M.; Ezure, T.; Shikata, M.; Ando, E.; Utsumi, T.; Tsunasawa, S.; Nishimura, O.
Protein prenylation in an insect cell-free protein synthesis system and identification of products by mass spectrometry
Proteomics
7
1942-1950
2007
Homo sapiens
Manually annotated by BRENDA team
Chen, S.; Fu, L.; Raja, S.M.; Yue, P.; Khuri, F.R.; Sun, S.Y.
Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis
Mol. Cancer
9
23
2010
Homo sapiens
Manually annotated by BRENDA team
Rao, P.V.; Peterson, Y.K.; Inoue, T.; Casey, P.J.
Effects of pharmacologic inhibition of protein geranylgeranyltransferase type I on aqueous humor outflow through the trabecular meshwork
Invest. Ophthalmol. Vis. Sci.
49
2464-2471
2008
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Ghavami, S.; Mutawe, M.; Schaafsma, D.; Yeganeh, B.; Unruh, H.; Klonisch, T.; Halayko, A.
Geranylgeranyl transferase 1 modulates autophagy and apoptosis in human airway smooth muscle
Am. J. Physiol. Lung Cell Mol. Physiol.
302
L420-L428
2012
Homo sapiens
Manually annotated by BRENDA team
Zhou, X.; Qian, J.; Hua, L.; Shi, Q.; Liu, Z.; Xu, Y.; Sang, B.; Mo, J.; Yu, R.
Geranylgeranyltransferase I promotes human glioma cell growth through Rac1 membrane association and activation
J. Mol. Neurosci.
49
130-139
2013
Homo sapiens
Manually annotated by BRENDA team
Shen, M.; Pan, P.; Li, Y.; Li, D.; Yu, H.; Hou, T.
Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling
Drug Discov. Today
20
267-276
2015
Homo sapiens (P49354), Homo sapiens (P53609), Rattus norvegicus (P53610), Rattus norvegicus (Q04631)
Manually annotated by BRENDA team
Gao, S.; Yu, R.; Zhou, X.
The role of geranylgeranyltransferase I-mediated protein prenylation in the brain
Mol. Neurobiol.
53
6925-6937
2015
Homo sapiens (P49354), Homo sapiens (P53609), Rattus norvegicus (P53610), Rattus norvegicus (Q04631), Mus musculus (Q61239), Mus musculus (Q8BUY9)
Manually annotated by BRENDA team
Lu, J.; Yoshimura, K.; Goto, K.; Lee, C.; Hamura, K.; Kwon, O.; Tamanoi, F.
Nanoformulation of geranylgeranyltransferase-I inhibitors for cancer therapy: liposomal encapsulation and pH-dependent delivery to cancer cells
PLoS ONE
10
e0137595
2015
Homo sapiens (P49354), Homo sapiens (P53609), Homo sapiens
Manually annotated by BRENDA team
Mansha, M.; Kumari, U.U.; Cournia, Z.; Ullah, N.
Pyrazole-based potent inhibitors of GGT1 Synthesis, biological evaluation, and molecular docking studies
Eur. J. Med. Chem.
124
666-676
2016
Homo sapiens (P49354 and P49356)
Manually annotated by BRENDA team