Information on EC 2.5.1.59 - protein geranylgeranyltransferase type I

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.5.1.59
-
RECOMMENDED NAME
GeneOntology No.
protein geranylgeranyltransferase type I
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
enzyme and geranylgeranyl diphosphate produce a stable binary complex and the tightly bound geranylgeranyl diphosphate is transferred to a peptide acceptor, without the equilibration of enzyme-bound geranylgeranyl diphosphate with free geranylgeranyl diphosphate
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
enzyme and geranylgeranyl diphosphate produce a stable binary complex and the tightly bound geranylgeranyl diphosphate is transferred to a peptide acceptor, without the equilibration of enzyme-bound geranylgeranyl diphosphate with free geranylgeranyl diphosphate; random sequential mechanism; 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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
random sequential mechanism; 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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
an ordered binding mechanism for enzyme where geranylgeranyl diphosphate adds before peptide; 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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
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, but 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 g-subunits of heterotrimeric G proteins and Ras-related GTPases such as members of the Ras and Rac/Rho families; 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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
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
-
geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
CAAX geranylgeranyltransferase
-
-
-
-
CaGGTase-I
Q9Y765
-
geranylgeranyl protein transferase type I
-
-
-
-
geranylgeranyltransferase I
-
-
geranylgeranyltransferase type I
-
-
geranylgeranyltransferase type I
-
-
geranylgeranyltransferase type I
-
-
geranylgeranyltransferase-1
-
-
-
-
geranylgeranyltransferase-I
Q9Y765
-
geranylgeranyltransferaseI
-
-
-
-
GGT I
-
-
GGTase
-
type I enzyme
GGTase-I
-
-
-
-
GGTase-I
Q94765
-
GGTase-I
-
-
GGTase-I
-
-
GGTaseI
-
-
-
-
mammalian GGTase-I
-
-
PGGT
-
-
-
-
PGGT-I
-
-
-
-
PGGT-I
Q6EZ49
-
PGGTaseI
-
-
-
-
protein geranylgeranyltransferase
-
-
-
-
protein geranylgeranyltransferase I
-
-
-
-
protein geranylgeranyltransferase type I
Q94765
-
protein geranylgeranyltransferase type I
-
-
protein geranylgeranyltransferase type I
-
-
protein geranylgeranyltransferase type I
-
-
protein geranylgeranyltransferase type I
-
-
protein geranylgeranyltransferase type-I
-
-
protein geranylgeranyltransferase-I
-
-
protein geranylgeranyltransferase-I
-
-
type I protein geranylgeranyltransferase
-
-
CAS REGISTRY NUMBER
COMMENTARY
135371-29-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain SC5314
UniProt
Manually annotated by BRENDA team
alpha-subunit
SwissProt
Manually annotated by BRENDA team
beta-subunit
SwissProt
Manually annotated by BRENDA team
enzyme produced in Sf9cells using baculovirus system
-
-
Manually annotated by BRENDA team
enzyme produced in Sf9cells using baculovirus system
-
-
Manually annotated by BRENDA team
type I enzyme
-
-
Manually annotated by BRENDA team
strains YOT433-2C, YOT434-2B, YOT435-1A, YOT436-3C, YOT437-2C
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
pharmacological inhibition of protein geranylgeranyltransferase-I induces simultaneous p53-dependent apoptosis and autophagy in airway smooth muscle cells, and autophagy regulates apoptosis induction
physiological function
-
enzyme GGTase-I is abundantly expressed in human primary glioma tissues. Inhibition or downregulation of GGTase-I markedly decreases the proliferation of glioma cells and induces their apoptosis, while overexpression of GGTase-I promotes cell growth in vitro. Inactivation of GGTase-I eliminates geranylgeranylation of RhoA and Rac1, prevents them from targeting to the plasma membrane, and inhibits Rac1 activity. Overexpressing wild type or constitutively active Rac1 stimulates glioma cell growth, similar to the effect of GGTase-I overexpression. Overexpressing dominant-negative Rac1 or Rac1 with the prenylation site deleted or mutated abrogates GGTase-I-induced proliferation in glioma cells
physiological function
-
inhibition or down-regulation using small interference RNA inhibits dendritic development of Purkinje cells. In contrast, up-regulation of enzyme expression promotes dendritic arborization of Purkinje cells. Neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor BDNF promotes membrane association of Rac1 and dendritic development of Purkinje cells in cultured cerebellar slices. The effect of BDNF or high K+ is inhibited by inhibition or down-regulation of enzyme
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 + (biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFF-S-farnesyl-CAI-Leu
show the reaction diagram
-
biotin-gamma6
-
-
?
farnesyl diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFF-S-farnesyl-CAI-Leu
show the reaction diagram
-
ECB-gamma6
-
-
?
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
-
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, substrate motif: carboxy-terminal -Ca1a2X box
-
-
?
geranylgeranyl diphosphate + (biotin-CONH-(CH2)5-CO-)-ALEPPETEPKRKCCI-Phe
diphosphate + (biotin-CONH-(CH2)5-CO-)-ALEPPETEPKRK-S-geranylgeranyl-CCI-Phe
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + (biotin-CONH-(CH2)5-CO-)-ALEPPETEPKRKCCI-Phe
diphosphate + (biotin-CONH-(CH2)5-CO-)-ALEPPETEPKRK-S-geranylgeranyl-CCI-Phe
show the reaction diagram
-
ECB-G25K, 42% activity in comparison of protein substrate motif: CAA-leucine
-
-
?
geranylgeranyl diphosphate + (biotin-CONH-(CH2)5-CO-)-GTPRASNRSCAIS
diphosphate + (biotin-CONH-(CH2)5-CO-)-GTPRASNRS-S-geranylgeranyl-CAIS
show the reaction diagram
-
ECB-laminB(S), 5% activity in comparison of protein substrate motif: CAA-leucine
-
-
?
geranylgeranyl diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFF-S-geranylgeranyl-CAI-Leu
show the reaction diagram
-
biotin-gamma6, preferred substrate
-
-
?
geranylgeranyl diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
diphosphate + (biotin-CONH-(CH2)5-CO-)-NPFREKKFF-S-geranylgeranyl-CAI-Leu
show the reaction diagram
-
ECB-gamma6, preferred substrate
-
-
?
geranylgeranyl diphosphate + Arg-Arg-Cys-Val-Leu-Leu
diphosphate + Arg-Arg-S-geranylgeranyl-Cys-Val-Leu-Leu
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
-
-
-
-
?
geranylgeranyl diphosphate + Cys-Val-Leu-Leu
S-geranylgeranyl-Cys-Val-Leu-Leu + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Cys-Val-Leu-Ser
S-geranylgeranyl-Cys-Val-Leu-Ser + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + dansyl-Cys-Ile-Ile-Leu
diphosphate + dansyl-S-geranylgeranyl-Cys-Ile-Ile-Leu
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + dansyl-Thr-Lys-Cys-Val-Ile-Met
diphosphate + dansyl-Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Met
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + glutathione S-transferase-GCVKIKKCVIL
diphosphate + ?
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + GST-CDC42
diphosphate + GST-S-geranylgeranyl-CDC42
show the reaction diagram
-
recombinant glutathione S-transferase fusion protein of CDC42Hs with a C-terminal Cys-Cys-Ile-Phe sequence
-
-
?
geranylgeranyl diphosphate + GST-RhoA
diphosphate + GST-S-geranylgeranyl-RhoA
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + H-Ras-CVLL
S-geranylgeranyl-protein + ?
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Ki-Ras4A
diphosphate + S-geranylgeranyl-Ki-Ras4A
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Ki-Ras4B
diphosphate + S-geranylgeranyl-Ki-Ras4B
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Ki-Ras4B
diphosphate + S-geranylgeranyl-Ki-Ras4B
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Leu-Pro-Cys-Val-Val-Met
diphosphate + Leu-Pro-S-geranylgeranyl-Cys-Val-Val-Met
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Lys-Lys-Cys-Ile-Ile-Met
diphosphate + Lys-Lys-S-geranylgeranyl-Cys-Ile-Ile-Met
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + N-dansyl-Gly-Cys-Val-Ile-Leu-OH
?
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + N-Ras
diphosphate + S-geranylgeranyl-N-Ras
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Phe-Phe-Cys-Ala-Ile-Leu
diphosphate + Phe-Phe-S-geranylgeranyl-Cys-Ala-Ile-Leu
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
A7Y1U8, -
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
Q94765
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
the Rab protein Rab8-GTPase, which ends with a Cys-Val-Leu-Leu motif is able to serve as a substrate for either geranylgeranyl transferase I and II, but modified predominantly by geranylgeranyl transferase II, Y78D mutation selective prevents prenylation of Rab8 by geranylgeranyl transferase II, but not geranylgeranyltransferaseI
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
prenylation, substrates are Rho, Rac, most trimeric G protein gamma subunits
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X. X is Leu, Phe or Ser, preferred substrate: Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X. X is Leu, Phe or Ser, preferred substrate: Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X. X is Leu, Phe or Ser, preferred substrate: Leu
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X. X is Leu or Phe
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X. X is Leu or Phe
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme requires that protein substrates contain a Cys residue fourth from the C terminus, protein substrate motif: Cys-aliphatic-aliphatic-X. X may be Leu, Phe, or Ser, with high concentrations of peptide substrates this specificity is lost
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme catalyses the transfer of the 20-carbon prenyl group from geranylgeranyl diphosphate to the cysteine residue near the C-termini of a variety of eukaryotic proteins
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
this prenylation is necessary for many proteins to interact with membrane localized at proper intracellular sites
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
this prenylation is necessary for many proteins to interact with membrane localized at proper intracellular sites
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
yeast enzyme is essential for yeast cell growth
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
GGTase-I catalyzes C-terminal lipidation of more than 100 proteins, including many GTP-binding regulatory proteins
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
the enzyme negatively regulates abscisic acid signaling in guard cells. The enzyme is specifically involved in negative regulation of auxin-induced lateral root initiation
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
substrate motif: carboxy-terminal -Ca1a2X box
-
-
?
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 + Ras protein
S-geranylgeranyl-Ras protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Ras-CVLL
S-geranylgeranyl-Ras-CVLL + diphosphate
show the reaction diagram
-
tritium labelled geranylgeranyl diphosphate for enzyme assay, His-tagged geranylgeranyl diphosphate
-
-
?
geranylgeranyl diphosphate + Ras-Cys-Val-Leu-Leu
diphosphate + Ras-S-geranylgeranyl-Cys-Val-Leu-Leu
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Ras-Cys-Val-Leu-Leu
diphosphate + Ras-S-geranylgeranyl-Cys-Val-Leu-Leu
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + RhoA
diphosphate + S-geranylgeranyl-RhoA
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + rhoC protein
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + S-geranylgeranyl-Ki-Ras4B
diphosphate + S-geranylgeranyl-Ki-Ras4B
show the reaction diagram
-
both the polylysine and the carboxy-terminal methionine are important for geranylgeranylation of this substrate
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Ala
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Ala
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Arg
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Arg
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Asn
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Asn
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Asp
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Asp
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Cys
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Cys
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Gln
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Gln
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Ile
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Ile
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Leu
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Leu
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Met
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Met
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Phe
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Phe
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Ser
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Ser
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Thr
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Thr
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Tyr
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Tyr
show the reaction diagram
-
-
-
-
?
Ser-Ser-Cys-Ile-Leu-Leu + geranylgeranyl diphosphate
diphosphate + Ser-Ser-S-geranylgeranyl-Cys-Ile-Leu-Leu
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Thr-Lys-Cys-Val-Ile-Val
diphosphate + Thr-Lys-(S-geranylgeranyl)-Cys-Val-Ile-Val
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
requires geranylgeranylation of rho1p for the correct function of enzyme
-
-
-
additional information
?
-
-
not: N-Ras
-
-
-
additional information
?
-
-
some of the 18 analysed hexapeptides effieciently farnsylated by enzyme
-
-
-
additional information
?
-
A7Y1U8, -
most of the CaaX-containing proteins with X= Leu and X= Met are good substrates of PGGT-I, whereas those with X= Phe are poor substrates for PGGT-I, Trypanosma cruzi j2 DNAJ protein, Trypanosoma cruzi PRL-1 protein tyrosine phosphatase, CHFM (a small GTPase like protein), and Trypanosoma cruzi Rho1 GTPase are no substrates for PGGT-I
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
Q94765
-
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
enzyme catalyses the transfer of the 20-carbon prenyl group from geranylgeranyl diphosphate to the cysteine residue near the C-termini of a variety of eukaryotic proteins
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
this prenylation is necessary for many proteins to interact with membrane localized at proper intracellular sites
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
this prenylation is necessary for many proteins to interact with membrane localized at proper intracellular sites
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
yeast enzyme is essential for yeast cell growth
-
-
-
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
GGTase-I catalyzes C-terminal lipidation of more than 100 proteins, including many GTP-binding regulatory proteins
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
the enzyme negatively regulates abscisic acid signaling in guard cells. The enzyme is specifically involved in negative regulation of auxin-induced lateral root initiation
-
-
?
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 + Ras protein
S-geranylgeranyl-Ras protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Ras-CVLL
S-geranylgeranyl-Ras-CVLL + diphosphate
show the reaction diagram
-
tritium labelled geranylgeranyl diphosphate for enzyme assay, His-tagged geranylgeranyl diphosphate
-
-
?
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Cd2+
-
the zinc in enzyme can be replaced by Cd2+
Cd2+
-
80% of maximal activity in the presence of 0.5 mM alone; the zinc in enzyme can be replaced by Cd2+
Cd2+
-
Cd-substituted enzyme has altered specificities with regard to utilization of both peptide and isoprenoid substrates; the zinc in enzyme can be replaced by Cd2+
Mg2+
-
no requirement
Mg2+
-
20% of maximal activity in the presence of 0.5 mM alone
Mg2+
-
no requirement
Mg2+
-
requirement, optimal activity at 0.5 mM in presence of 0.1 mM Zn2+
Mg2+
-
required, optimal activity of EDTA-treated enzyme at 0.5 mM, Mg2+ probably activates the diphosphate leaving group of enzyme, and is essential for transferring the bound peptide substrate
Mg2+
-
prenylation rate constant of wild type enzyme is not dependent on Mg2+ and is about 20fold slower than the maximal rate constant catalyzed by protein farnesyltransferase. Prenylation rate constant in mutant Kbeta311A or Kbeta311D decreases in absence of magnesium 941fold without significantly affecting the binding affinityof either substrate. Furthermore, the geranylgeranylation rate constant is enhanced by the addition of Mg2+ for Kbeta311A and Kbeta311D GGTase I 25-fold compared with wild type GGTase I. These results demonstrate that lysine beta311 of GGTase I partially replaces the catalytic function of Mg2+ observed in protein farnesyltransferase
Mg2+
Q94765
for maximum reaction rate
Zinc
-
all of the GGTase-I complexes contain a zinc ion bound at full occupancy with a B-factor comparable with the surrounding protein residues. The zinc ion is coordinated by three residues, Asp269b, Cys271b and His321b
Zn2+
-
A zinc metalloenzyme. The Zn2+ is required for peptide, but not for isoprenoid, substrate binding
Zn2+
-
required, but no activity in presence of Zn2+ alone, only when either 0.1 mM Mg2+, Mn2+ or Cd2+ is additionally present
Zn2+
-
enzyme contains a single zinc atom
Zn2+
-
A zinc metalloenzyme. The Zn2+ is required for peptide, but not for isoprenoid, substrate binding
Zn2+
-
enzyme contains tightly bound Zn2+ which is required for its catalytic activity
Zn2+
-
requirement, optimal activity of EDTA-treated enzyme at 0.01 mM in presence of 1 mM Mg2+
Zn2+
-
catalytic zinc ion coordinates the thiol of the peptide substrate
Zn2+
-
required for catalysis and peptide binding, one zinc ion per protein dimer
Zn2+
Q94765
activating the cysteine thiolate of the substrate
Mn2+
-
60% of maximal activity in the presence of 0.5 mM alone
additional information
-
metals not needed for complex formation between enzyme and geranylgeranyl diphosphate, but addition of prenyl acceptor only results in prenyl transfer in presence of Mg2+ and Zn2+; not: Co2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2R,3R,4S,5R)-2-(3,4-dichlorophenyl)-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-1-[(4-methylphenyl)sulfonyl]-4-(pentylsulfanyl)-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-[(4-methoxyphenyl)sulfanyl]-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-5-ethyl-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-5-hexyl-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(3-chlorophenyl)-5-(cyclopentylmethyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(4-chlorophenyl)-1-[(4-chlorophenyl)sulfonyl]-5-(cyclopentylmethyl)pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(4-chlorophenyl)-5-(cyclopentylmethyl)-1-(phenylsulfonyl)pyrrolidine-3-carboxylic acid
-
-
(2S,5R)-5-ethyl-2-(4-fluorophenyl)-1-tosyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid
-
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
-
IC50: 0.0005 mM using RhoA as a substrate, IC50: 0.0009 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
-
-
(2S,6S)-2,6-bis(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid
-
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
-
IC50: 0.12 mM using RhoA as a substrate, IC50: 0.08 mM using Ki-Ras4B as a substrate
(S)-N-(4-(3,4-dichlorophenoxy)benzyl)-6-(1H-indol-3-yl)piperazine-2,5-dione
-
dual inhibitor for both farnesyl transferase and geranygeranyltransferase-I. Compound occupies both isoprenoid and peptide substrate binding sites
(S)-N-(4-(3-chlorophenoxy)benzyl)-6-(1H-indol-3-yl)piperazine-2,5-dione
-
dual inhibitor for both farnesyl transferase and geranygeranyltransferase-I
1-phosphono-(E,E,E)-geranylgeraniol
-
competitive to geranylgeranyl diphosphate, noncompetitive to GST-CDC42
1-phosphono-(E,E,E)-geranylgeraniol
-
competitive to geranylgeranyl diphosphate, potent substrate inhibition to dansyl-Gly-Cys-Ile-Ile-Leu
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
11-aminoundecylcarbonyl-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
competitive. bivalent inhibitor for simultaneous recognition of both exteriorand interior protein surface. Not inhibitory against farnesyltransferase
2-aryl-4-aminobenzoic acid
-
IC50: 21 nM
2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-N-(3-methyl-butyl)-acetamide
-
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
-
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
-
0.1 mM, 78.6% inhibition
3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid ethyl ester
-
0.1 mM, 3% inhibition
3-(4'-geranyloxy-3'-OH-phenyl)-2-trans propenoic acid
-
0.1 mM, 72.4% inhibition
3-(4'-geranyloxy-3'-OH-phenyl)-2-trans propenoic acid ethyl ester
-
0.1 mM, 7.5% inhibition
3-(4'-isopentenyloxy-3'-OH-phenyl)-2-trans propenoic acid
-
0.1 mM, 46.4% inhibition
3-aza-geranylgeranyl-diphosphate
-
competitive inhibitor with respect to geranylgeranyl diphosphate, non-competitive to Cys-Val-Phe-Leu
3-chloro-N-[2-oxo-2-[2-[[1-phenyl-3-(4-propoxyphenyl)pyrazol-4-yl]methylidene]hydrazinyl]ethyl]benzamide
-
GGTI-DU.Sig1, PubChem CID 3311883, inhibitor of protein geranylgeranyltransferase type I
4-[[([5-[(4-ethylphenoxy)methyl]-4-(1-phenylethyl)-4H-pyrazol-3-yl]sulfanyl)acetyl]amino]benzamide
-
inhibitor identified using quantitative structure-activity realtionship models and virtual screening of chemicals. confirmation of predicted data by experiment
4-[[2-[[5-(2-methoxyphenyl)-4-phenethyl-1,2,4-triazol-3-yl]sulfanyl]acetyl]amino]benzamide
-
GGTI-DU.En1, PubChem CID 2118978, inhibitor of protein geranylgeranyltransferase type I
4-[[2-[[5-[(4-ethylphenoxy)methyl]-4-(1-phenylethyl)-1,2,4-triazol-3-yl]sulfanyl]acetyl]amino]benzamide
-
GGTI-DU.En2, PubChem CID 3455185, inhibitor of protein geranylgeranyltransferase type I, no or little activity against protein farnesyltransferase
auraptene
-
0.1 mM, 18.6% inhibition
boropinic acid
-
0.1 mM, 31% inhibition
collinin
-
0.1 mM, 34.2% inhibition
Cys-3-(aminomethyl)benzoic acid-Leu
-
noncompetitive to geranylgeranyl diphosphate, competitive to dansyl-Gly-Cys-Ile-Ile-Leu
Cys-Val-Phe-Leu
-
noncompetitive inhibitor with respect to geranylgeranyl diphosphate, 50% inhibition at 0.0001 mM, competitive to Cys-Val-Phe-Leu
diethyl dicarbonate
-
80% loss of activity at 5 mM
GGTI-2151
A7Y1U8, -
16.3% inhibition at 50 nM
GGTI-2154
A7Y1U8, -
14.7% inhibition at 50 nM
GGTI-298
-
induces apoptosis and augments tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. GGTI-298 induces DR4 and DR5 expression and reduces c-FLIP levels. Enforced c-FLIP expression or DR5 knockdown attenuates apoptosis induced by GGTI-298 and TRAIL combination. DR4 knockdown sensitizes cancer cells to GGTI298/TRAIL-induced apoptosis. The combination of GGTI-298 and TRAIL is more effective than each single agent in decreasing the levels of IkappaBalpha and p-Akt
GGTI-298
-
treatment of airway smooth muscle cells induces expression of p53-dependent proteins, p53 upregulated modulator of apoptosis Noxa, and damage-regulated autophagy modulator DRAM, this is inhibited by the p53 transcriptional activation inhibitor cyclic-pifithrin-alpha. Inhibition of autophagy with bafilomycin-A1 or short-hairpin RNA silencing of Atg7 substantially augments GGTI-298-induced apoptosis
GGTI-DU40
A7Y1U8, -
16.3% inhibition at 50 nM
GGTI-DU40
-
1-40 microM dissolved in dimethyl sulfoxide, affects actin cytoskeletal integrity, cell adhesion, cell-cell junctions, myosin II phosphorylation, and membrane localization of GTP-binding proteins in trabecular meshwork cells is tested using immunofluorescence detection and immunoblotting analysis and the effect on aqueous humor outflow
GGTI-DU40
-
5-40 microM dissolved in dimethyl sulfoxide influence cell morphology in a dose and time dependent manner, affects actin cytoskeletal integrity, cell adhesion, cell-cell junctions, myosin II phosphorylation, and membrane localization of GTP-binding proteins in trabecular meshwork cells is tested using immunofluorescence detection and immunoblotting analysis and the effect on aqueous humor outflow (25 and 40 microM)
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)
-
-
N-(2,5-dichlorophenyl)-N'-[[3-(4-methylphenyl)-1-phenylpyrazol-4-yl]methylideneamino]oxamide
-
GGTI-DU.Sig2, PubChem CID 4277701, inhibitor of protein geranylgeranyltransferase type I
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)
-
-
N-benzyl-2-[(2-chlorobenzyl)[[5-(4-methylphenyl)-2H-tetrazol-2-yl]acetyl]amino]butanamide
-
inhibitor identified using quantitative structure-activity realtionship models and virtual screening of chemicals. confirmation of predicted data by experiment
N-benzyl-2-[(2-chlorophenyl)methyl-[2-[5-(4-methylphenyl)tetrazol-2-yl]acetyl]amino]butanamide
-
GGTI-DU.As2, PubChem CID 3180738, inhibitor of protein geranylgeranyltransferase type I, no or little activity against protein farnesyltransferase
N-[(E)-1-(benzylcarbamoyl)-2-[5-(3,4-dichlorophenyl)furan-2-yl]ethenyl]-4-methylbenzamide
-
inhibitor identified using quantitative structure-activity realtionship models and virtual screening of chemicals. confirmation of predicted data by experiment
N-[12-([[3,4,5-tris(3-ammoniopropoxy)phenyl]carbonyl]amino)dodecanoyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
-
-
N-[2-(benzylamino)-2-oxoethyl]-2-[5-(4-chlorophenyl)tetrazol-2-yl]-N-(4-propan-2-ylphenyl)acetamide
-
GGTI-DU.As1, PubChem CID 3180720, inhibitor of protein geranylgeranyltransferase type I
N-[3-(benzylamino)-1-[5-(3,4-dichlorophenyl)furan-2-yl]-3-oxoprop-1-en-2-yl]-4-methylbenzamide
-
GGTI-DU.Sig3, PubChem CID 5143450, inhibitor of protein geranylgeranyltransferase type I, no or little activity against protein farnesyltransferase
N-[6-(3,4,5-tris(3-amino-1-propoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
competitive, bivalent inhibitor for simultaneous recognition of both exterior and interior protein surface. Not inhibitory against farnesyltransferase
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-hexylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
-
-
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-propylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
bivalent inhibitor for simultaneous recognition of both exterior and interior protein surface. Not inhibitory against farnesyltransferase
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
competitive, bivalent inhibitor for simultaneous recognition of both exterior and interior protein surface. Not inhibitory against farnesyltransferase
NPFREKKFFCAIL
-
biotin-gamma6, substrate inhibition at high peptide concentration
PD-083176
-
noncompetitive to geranylgeranyl diphosphate, competitive to GST-CDC42, modest inhibitor
-
Phenylglyoxal
-
80% loss of activity, inactivation of inhibition in the presence of geranylgeranyl diphosphate
Thr-Lys-Cys-Val-Ile-Leu
-
potent competitor, 50% inhibition at 0.001 mM
Thr-Lys-Cys-Val-Ile-Met
-
potent competitor, 50% inhibition at 0.008 mM
umbelliprenine
-
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
L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
additional information
-
TKSer-Val-Ile-Leu inactive as competitor
-
additional information
-
not inhibited by valencic acid, 4'-geranyloxybenzoic acid, 4-isopentenyloxy-3-methoxy benzoic acid, and 4-geranyloxy-3-methoxy benzoic acid
-
additional information
-
not inhibited by 3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoic acid methyl ester trifluoroacetate and mono(3,3',3''-(5-(methoxycarbonyl)benzene-1,2,3-triyl)tris(oxy)tripropan-1-aminium) mono(2,2,2-trifluoroacetate)
-
additional information
A7Y1U8, -
the mammalian PGGT-I inhibitors GGTI-297 and FTI-276 have little effect on Trypanosoma cruzi PGGT-I activity
-
additional information
-
inhibitors pose a potential treatment for inflammation, multiple sclerosis, atherosclerosis, and other diseases, 47 potential inhibitors with a predicted IC50 greater than 5.50 microM are identified by the use of quantitative structure-activity relationship models and in vitro tests with 7 of them
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
7-isopentenyloxycoumarin
-
0.1 mM, 10.3% activation
additional information
-
PGGT-I is specifically required for the jasmonic acid signalling triggering octadecanoid-derivative responsive Catharanthus AP2 domain 3 expression
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00027
-
(biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
-
pH 7.0, 30C, prenyl donor: geranylgeranyl diphosphate
-
0.0078
-
(biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
-
pH 7.0, 30C, prenyl donor: farnesyl diphosphate
-
0.025
-
(biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
-
pH 7.0, 30C, prenyl donor: geranylgeranyl diphosphate
-
0.00003
-
3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]-oxadiazo-4-ylamino)-dodeca-2,6,10-trien-1-diphosphate
-
-
0.00002
-
Arg-Arg-Cys-Val-Leu-Leu
-
pH 7.6, 30C
0.00000133
-
Asp-Asp-Pro-Thr-Ala-Ser-Ala-Cys-Val-Leu-Leu
-
at 30C
0.0018
-
dansyl-Gly-Cys-Ile-Ile-Leu
-
pH 7.5, 30C
0.0024
-
dansyl-Gly-Cys-Ile-Ile-Leu
-
pH 7.5, 30C
0.000003
-
geranylgeranyl diphosphate
-
pH 7.7, 30C
0.00001
-
geranylgeranyl diphosphate
-
pH 7.5, 37C
0.00003934
-
geranylgeranyl diphosphate
-
at 30C
0.00094
-
geranylgeranyl diphosphate
-
pH 7.5, 30C
0.001
-
geranylgeranyl diphosphate
-
pH 7.5, 30C
0.00143
-
glutathione S-transferase-GCVKIKKCVIL
-
pH 7.5, 37C
-
0.016
-
GST-CDC42
-
pH 7.0, 30C, prenyl donor: geranylgeranyl diphosphate
-
0.042
-
GST-RhoA
-
-
-
0.0088
-
Ki-Ras4A
-
pH 7.5, 37C
-
0.012
-
Ki-Ras4B
-
pH 7.5, 37C
-
0.00013
-
Lys-Lys-Cys-Ile-Ile-Met
-
pH 7.6, 30C
0.0021
-
N-Ras
-
pH 7.5, 37C
-
0.002
-
Phe-Phe-Cys-Ala-Ile-Leu
-
pH 7.6, 30C
-
0.0009
-
Ras-Cys-Val-Leu-Leu
-
pH 7.5, 37C
-
0.0012
-
Ras-Cys-Val-Leu-Leu
-
pH 7.7, 30C
-
0.0002
-
Ser-Ser-Cys-Ile-Leu-Leu
-
pH 7.4, 30C
0.002
-
Lys-Pro-Cys-Val-Val-Met
-
pH 7.6, 30C
additional information
-
additional information
-
comparison of Km of CAAX-substrates with X is Leu, Phe or Ser
-
additional information
-
additional information
-
comparison of Km of wild-type and mutant enzyme
-
additional information
-
additional information
-
comparison of Km of 18 hexapeptides as potential substrates of the farnesyltransferase and geranylgeranyl transferaseI, recognition of overlapping sequences by farnesyltransferase and geranylgeranyltransferaseI
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.028
-
(biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
-
prenyl donor: geranylgeranyl diphosphate
-
0.1
-
(biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
-
prenyl donor: farnesyl diphosphate
-
0.12
-
(biotin-CONH-(CH2)5-CO-)-NPFREKKFFCAI-Leu
-
prenyl donor: geranylgeranyl diphosphate
-
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 30C
0.02
-
geranylgeranyl diphosphate
-
-
0.021
-
geranylgeranyl diphosphate
-
at 30C
0.34
-
geranylgeranyl diphosphate
-
-
0.0057
-
GST-CDC42
-
prenyl donor: geranylgeranyl diphosphate
-
0.08
-
GST-RhoA
-
-
-
0.0667
-
Ki-Ras4A
-
-
-
0.0113
-
N-Ras
-
-
-
0.014
-
Ras-Cys-Val-Leu-Leu
-
-
-
0.02
-
Ras-Cys-Val-Leu-Leu
-
-
-
0.001
-
Thr-Lys-Cys-Val-Ile-Ala
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.001
-
Thr-Lys-Cys-Val-Ile-Arg
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.001
-
Thr-Lys-Cys-Val-Ile-Asn
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.001
-
Thr-Lys-Cys-Val-Ile-Asp
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.0063
-
Thr-Lys-Cys-Val-Ile-Cys
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.001
-
Thr-Lys-Cys-Val-Ile-Gln
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.048
-
Thr-Lys-Cys-Val-Ile-Ile
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.088
-
Thr-Lys-Cys-Val-Ile-Leu
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.082
-
Thr-Lys-Cys-Val-Ile-Met
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.06
-
Thr-Lys-Cys-Val-Ile-Phe
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.001
-
Thr-Lys-Cys-Val-Ile-Ser
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.001
-
Thr-Lys-Cys-Val-Ile-Thr
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.022
-
Thr-Lys-Cys-Val-Ile-Tyr
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.107
-
Thr-Lys-Cys-Val-Ile-Val
-
in 50 mM Tris-HCl, 5 mM dithiothreitol, 5 mM MgCl2, and 0.01 mM ZnCl2
0.0767
-
Ki-Ras4B
-
-
-
additional information
-
additional information
-
comparison of kcat of CAAX-substrates with X is Leu, Phe or Ser
-
additional information
-
additional information
-
comparison of kcat of wild-type and mutant enzyme
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00086
-
1-P-GGOH
-
with respect to GST-CDC42
0.0002
-
1-phosphono-(E,E,E)-geranylgeraniol
-
with respect to geranylgeranyl diphosphate
0.00072
-
1-phosphono-(E,E,E)-geranylgeraniol
-
with respect to geranylgeranyl diphosphate
0.000015
-
3-aza-geranylgeranyl-diphosphate
-
with respect to geranylgeranyl diphosphate
0.000022
-
3-aza-geranylgeranyl-diphosphate
-
with respect to Ras-Cys-Val-Leu-Leu
0.078
-
Cys-3-(aminomethyl)benzoicacid-Leu
-
with respect to dansyl-Gly-Cys-Ile-Ile-Leu
0.14
-
Cys-3-(aminomethyl)benzoicacid-Leu
-
with respect to geranylgeranyl diphosphate
0.00005
-
Cys-Val-Phe-Leu
-
with respect to Ras-Cys-Val-Leu-Leu
0.0082
-
PD-083176
-
with respect to GST-CDC42
-
0.0087
-
PD-083176
-
with respect to geranylgeranyl diphosphate
-
0.000065
-
Cys-Val-Phe-Leu
-
with respect to geranylgeranyl diphosphate
additional information
-
additional information
-
KI for varied concentrations of dansyl-Gly-Cys-Ile-Ile-Leu
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.25
4
(2S,5R)-5-ethyl-2-(4-fluorophenyl)-1-tosyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid
-
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
-
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
-
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
-
IC50: 0.12 mM using RhoA as a substrate, IC50: 0.08 mM using Ki-Ras4B as a substrate
0.021
-
(S)-N-(4-(3,4-dichlorophenoxy)benzyl)-6-(1H-indol-3-yl)piperazine-2,5-dione
-
pH 7.4, 30C
0.0323
-
(S)-N-(4-(3-chlorophenoxy)benzyl)-6-(1H-indol-3-yl)piperazine-2,5-dione
-
pH 7.4, 30C
0.006525
-
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid
-
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
-
IC50: above 0.01 mM
0.0014
-
11-aminoundecylcarbonyl-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
0.000021
-
2-aryl-4-aminobenzoic acid
-
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
-
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
-
IC50: above 0.01 mM
0.00017
-
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid
-
IC50: 170 nM
0.0063
-
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
0.0045
-
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
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
-
IC50: above 0.01 mM
0.00058
-
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid
-
IC50: 580 nM
0.0027
-
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
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
-
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
-
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
-
IC50: above 0.01 mM
0.008
-
4-[[([5-[(4-ethylphenoxy)methyl]-4-(1-phenylethyl)-4H-pyrazol-3-yl]sulfanyl)acetyl]amino]benzamide
-
30C
0.00007
-
GGTI-DU40
-
complete inhibition at 5 microM, tritium-labelled geranylgeranyl diphosphate for activity assay with lysate of trabecular mesh cells, 30C
0.0048
-
L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
0.0014
-
N-(12-ammoniododecanoyl)-D-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
-
-
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)
-
-
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)
-
-
0.035
-
N-benzyl-2-[(2-chlorobenzyl)[[5-(4-methylphenyl)-2H-tetrazol-2-yl]acetyl]amino]butanamide
-
30C
0.043
-
N-[(E)-1-(benzylcarbamoyl)-2-[5-(3,4-dichlorophenyl)furan-2-yl]ethenyl]-4-methylbenzamide
-
30C
0.0006
-
N-[12-([[3,4,5-tris(3-ammoniopropoxy)phenyl]carbonyl]amino)dodecanoyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
-
-
0.0006
-
N-[6-(3,4,5-tris(3-amino-1-propoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
0.00066
-
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-propylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
0.00064
-
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
0.00098
-
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
0.01
-
[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetic acid benzyl ester
-
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
-
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
-
IC50: above 0.01 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0059
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
enzyme is abundantly expressed in the developing rat cerebellum, in particular molecular layer, the region enriched with Purkinje cell dendrites
Manually annotated by BRENDA team
-
human trabecular meshwork cells, lysate for activity assay
Manually annotated by BRENDA team
-
porcine trabecular meshwork cells, freshly isolated, and organ culture
Manually annotated by BRENDA team
-
primary culture of airway smooth muscle cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37000
-
Q94765
alpha-subunit
42000
-
A7Y1U8, -
beta subunit of PGGT-I, SDS-PAGE
45000
-
Q94765
beta-subunit
82000
-
Q94765
heterodimer of the alpha and beta subunits
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
A7Y1U8, -
-
heterodimer
-
alpha,beta, 1 * 48000 + 1 * 43000
heterodimer
-
1 * 48000 + 1 * 40000
heterodimer
-
alpha,beta, 1 * 34000 + 1 * 42000
heterodimer
-
-
heterodimer
-
1 * 43000 + 1 * 48000
heterodimer
Q94765
1 * 37000 + 1 * 45000
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
side-chain modification
-
chemical modification with phenylglyoxal of arginine residue: 80% loss of activity in 30 min, chemical modification with diethyl dicarbonate of histidine residue: 80% loss of activity at 5 mM
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hanging-drop method, crystal structure of GGTase-I in complex with its cognate lipid substrate, geranylgeranylpyrophosphate
Q9Y765
enzyme in complex with its substrate geranylgeranylpyrophosphate, hanging drop method, PCB buffer, pH 7.0 and 25% PEG 1500, cryoprotection in PCB vuffer, pH 7.0, 30% PEG 1500, and 10% ethylene glycol, flash frozen in liquid nitrogen, diffraction data collection at -173C
Q94765
1. binary complex with geranylgeranyl diphosphate, 2. ternary complex with a non-hydrolyzable geranylgeranyl diphosphate analog and CaaX peptide, 3. binary complex with prenyl-peptide product and 4. ternary complex with prenylated product and geranylgeranyl diphosphate. GGTase-I crystals belong to the I222 space group, with three complete 91 kDa heterodimers in the asymmetric unit. GGTase-I crystals are grown at 17C in hanging drops using equal volumes of protein and reservoir solution (1.3 M (NH4)2SO4, 175 mM Na3 citrate pH 6.5, 20 mM dithiothreitol and 100 mM MES pH 6.3)
-
low-affinity ternary complex of L-778,123 bound in GGTase-I peptide-binding site and geranylgeranyl diphosphate bound in the lipid-binding site and complex of GGTase-I with L-778,123 and a sulfate anion
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.6
-
-
at pH 8.6 no enzyme activity is detected
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
no enzyme activity in the presence of EDTA
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
peptide affinity chromatography of enzyme on SSCILL-Sepharose
-
centrifugation of cells, frozen paste resuspended in 20 mM Tris, pH 7.7 with 5 mM dithiothreitol, and 5 microM ZnCls, and protease inhibitor tablet, cells lysed with pressure homogenization, crude lysate clarified by centrifugation, applied to DEAE Sepharose column, fractionation with buffer and varying NaCl concentrations, pooling of fractions, addition of substrate geranylgeranylpyrophosphate to displace nonspecifically bound lipids, phenyl-Sepharose column fractionation with gradient of buffer with (NH4)2SO4, pooled fractions applied to Q-Sepharose column, fractionated with gradient of buffer and NaCl, concentration of active fractions, application to a 120-ml Superdex 16/10 gel filtration column, concentration of enzyme
Q94765
nickel agarose resin chromatography
-
recombinant enzyme
-
recombinant enzyme
-
recombinant enzyme
-
recombinant wild-type and mutant enzymes
-
Q-Sepharose HP column chromatography and Superdex 200 gel filtration
A7Y1U8, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
PCR-amplification and expression in Escherichia coli
Q94765
expressed in Escherichia coli strain BL21(DE3) GGPT/pET23a
-
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
-
recombinant mammalian enzyme expressed in Sf9 cells
-
coexpression of two subunits of enzyme by Sf9 cells infected with recombinant baculovirus
-
expressed in Escherichia coli
-
alpha-subunit encoded by RAM2 and beta-subunit encoded by CDC43 translationally coupled by overlapping the RAM-CDC43 stop-start codons and by locating a ribosome-binding site near the 3' end of RAM2, recombinant enzyme overproduced in Escherichia coli
-
alpha-subunit encoded by RAM2 cloned to the pFC vector, which has an chloroamphenicol resistance gene and beta-subunit encoded by CAL1 cloned to the pFlag vector, which has an ampicillin resistance gene, these two recombinant enzymes are cotransformed and expressed in Escherichia coli
-
wild-type and mutant enzymes expressed in Escherichia coli
-
identification of the cwp1+ gene, which encodes the alpha-subunit of enzyme, coexpression of cwp1p and cwg2p, beta-subunit, in Escherichia coli
-
expressed in Sf9 insect cells
A7Y1U8, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Kbeta311A
-
mutation decreases prenylation rate constant in absence of Mg2+. Addition of Mg2+ increases geranylgeranylation rate constant
Kbeta311D
-
mutation decreases prenylation rate constant in absence of Mg2+. Addition of Mg2+ increases geranylgeranylation rate constant
D140N
-
alpha-subunit, increased Km
H145D
-
alpha-subunit, increased Km
N282A
-
alpha-subunit, increased Km
H216D
-
beta-subunit, KM of geranylgeranyl diphosphate increased 12fold
additional information
-
comparison of substrate specificity, using GST-CAIL and geranylgeranyl diphosphate: best substrate of wild-type enzyme, using GST-CVIM and geranylgeranyl diphosphate: best substrate of mutant beta H216D, using GST-CAIL and farnesyl diphosphate: best substrate of mutant betaR166I; seven different mutations in CAL1/CDC43 gene: cal1-1 and cdc43-2 to cdc43-7, all of mutants possess reduced activity and none show temperature-sensitive enzymatic activities, but all of them show temperature-sensitive growth phenotypes
additional information
-
cal1-1 mutation preferentially affects Rho1p geranylgeranylation, and it can be suppressed by Rho1p overexpression, the cdc43-5 mutation in the same gene causes accumulation of Cdc42p in soluble form and can be suppressed by Cdc42p overproduction; seven different mutations in CAL1/CDC43 gene: cal1-1 and cdc43-2 to cdc43-7, all of mutants possess reduced activity and none show temperature-sensitive enzymatic activities, but all of them show temperature-sensitive growth phenotypes
R166I
-
beta-subunit, KM of geranylgeranyl diphosphate increased 29fold, no forming of geranygeranyl diphosphate
additional information
-
Cwg2-1 mutant has a defect in the actin organization, this mutant is identified as a single nucleotide change causing an A202T substitution in a residue conserved among the beta-subunit of enzyme, the deletion of cwg2 causes cell death
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
potential target in anticancer drug research
medicine
-
inhibitor GGTI-298 induces apoptosis and augments tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. GGTI-298 induces DR4 and DR5 expression and reduces c-FLIP levels. Enforced c-FLIP expression or DR5 knockdown attenuates apoptosis induced by GGTI-298 and TRAIL combination. DR4 knockdown sensitizes cancer cells to GGTI298/TRAIL-induced apoptosis. The combination of GGTI-298 and TRAIL is more effective than each single agent in decreasing the levels of IkappaBalpha and p-Akt
medicine
-
enzyme GGTase-I is abundantly expressed in human primary glioma tissues. Inhibition or downregulation of GGTase-I markedly decreases the proliferation of glioma cells and induces their apoptosis, while overexpression of GGTase-I promotes cell growth in vitro. Inactivation of GGTase-I eliminates geranylgeranylation of RhoA and Rac1, prevents them from targeting to the plasma membrane, and inhibits Rac1 activity. Overexpressing wild type or constitutively active Rac1 stimulates glioma cell growth, similar to the effect of GGTase-I overexpression. Overexpressing dominant-negative Rac1 or Rac1 with the prenylation site deleted or mutated abrogates GGTase-I-induced proliferation in glioma cells
medicine
-
target for anti-cancer drugs
medicine
-
S-prenylated enzymes are interesting targets for noncytotoxic anticancer agents