Information on EC 2.5.1.60 - protein geranylgeranyltransferase type II

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
2.5.1.60
-
RECOMMENDED NAME
GeneOntology No.
protein geranylgeranyltransferase type II
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
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 I (EC 2.5.1.59), constitutes the protein prenyltransferase family of enzymes. Attaches geranylgeranyl groups to two C-terminal cysteines in Ras-related GTPases of a single family, the Rab family (Ypt/Sec4 in lower eukaryotes) that terminate in XXCC, XCXC and CCXX motifs. Reaction is entirely dependent on the Rab substrate being bound to Rab escort protein (REP). Post-translational modification with the geranylgeranyl moiety is essential for Rab GTPases to be able to control the processes of membrane docking and fusion [5].
CAS REGISTRY NUMBER
COMMENTARY hide
135371-29-8
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2E,6E,10Z)-3,7,11-trimethyl-12-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]dodeca-2,6,10-trien-1-yl diphosphate + Rab7 GTPase
(2E,6E,10Z)-3,7,11-trimethyl-12-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]dodeca-2,6,10-trien-1-yl-Rab7 GTPase + diphosphate
show the reaction diagram
-
in vitro prenylation assay with 4 microM Rab7 wild type or mutants, 6 mircoM Rab escort protein, 6 microM enzyme, 50 mM HEPES buffer, pH 7.2, containing 50 mM NaCl, 5 mM dithioerythritol, 2 mM MgCl2, and 10 mircoM GDP, 25°C, 50 microM of the geranylgeranyl diphosphate analogue (3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,10-triem-1) diphosphate, end-point assay with 6 microM Rab7 wild type or mutants, 10 microM Rab escort protein, 6 microM enzyme in the same buffer mixture, and 40 microM (3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,10-triem-1) diphosphate, 1.5 hours at 25°C
-
-
?
(3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate + Rab7
(3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1)-Rab7 + diphosphate
show the reaction diagram
-
geranylgeranyl diphosphate analogue and Rab7 as substrates in the presence of Rab escort protein, in vitro inhibition assays
-
-
?
biotinylated geranyl diphosphate + EYFP-Rab7
S-biotin-geranyl-Rab7 + diphosphate
show the reaction diagram
-
COS-7 cells are transfected with EYFP-Rab7 fusion protein and incubated with inhibitors, cells lysed after 24 h, clarified supernatant incubated in biotinylated geranyl diphosphate (geranylgeranyl diphosphate substrate analogue), recombinant RabGGTase and Rab escort protein, in vivo inhibitor studies
-
-
?
geranylgeranyl diphosphate + Arabidopsis thaliana RAB-ATa protein
S-geranylgeranyl-RAB GTPase + diphosphate
show the reaction diagram
-
homozygous insertion mutants (rgtb1-1 and rgtb1-2) of the major beta-subunit of Arabidopsis enzyme (RGTB1) lead to reduced enzyme activity (about 25%), 50 mM phosphate buffer, pH 7.6, 10 mM MgCl2, 5 mM DTT, 0.5 microM tritium-labelled all trans-geranylgeranyl pyrophosphate, 4 microg recombinant Arabidopsis thaliana RAB-A2a protein, 32°C, 40 min
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
geranylgeranyl diphosphate + Rab
S-geranylgeranyl-Rab + diphosphate
show the reaction diagram
-
His6- and gluthathione S-transferase-tagged Rab proteins such as canine Rab1a, human Rab27a, Rab5a, Rab18, Rab6a, Rab13, and mouse Rab23
-
-
?
geranylgeranyl diphosphate + Rab protein
S-geranylgeranyl-Rab protein + diphosphate
show the reaction diagram
geranylgeranyl diphosphate + Rab-protein-cysteine
S-geranylgeranyl-Rab-protein + diphosphate
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Rab1A
?
show the reaction diagram
-
substrate motif: -XXCC
-
-
?
geranylgeranyl diphosphate + Rab1B
?
show the reaction diagram
-
-
-
-
?
geranylgeranyl diphosphate + Rab3A
?
show the reaction diagram
-
substrate motif: -XCXC
-
-
?
geranylgeranyl diphosphate + Rab5A
?
show the reaction diagram
-
substrate motif: -CCXX
-
-
?
geranylgeranyl diphosphate + Rab7 protein
S-geranylgeranyl-Rab7 protein + diphosphate
show the reaction diagram
-
the N-terminal Cys207 is preferred to Cys205, activity with Rab7 mutants, overview
-
-
?
geranylgeranyl diphosphate + Rab8
?
show the reaction diagram
-
the Rab protein Rab8-GTPase, which end with a Cys-Val-Leu-Leu motif able to serve as a substrate for either geranylgeranyl transferase I and II, but modified predominantly by either geranylgeranyl transferase II in vitro, but the mutation of Y78D prevents Rab8 from serving as a substrate
-
-
?
geranylgeranyl diphosphate + Ypt1p
?
show the reaction diagram
[3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)dodeca-2,6,10-trien-1] diphosphate + Rab7 protein
?
show the reaction diagram
-
i.e. NBD-FPP, a fluorescent analogue of geranylgeranyl diphosphate, which is a lipid donor for RabGGTase
product is mono-NBD-farnesylated Rab7:REP-1 complex
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate + Arabidopsis thaliana RAB-ATa protein
S-geranylgeranyl-RAB GTPase + diphosphate
show the reaction diagram
-
homozygous insertion mutants (rgtb1-1 and rgtb1-2) of the major beta-subunit of Arabidopsis enzyme (RGTB1) lead to reduced enzyme activity (about 25%), 50 mM phosphate buffer, pH 7.6, 10 mM MgCl2, 5 mM DTT, 0.5 microM tritium-labelled all trans-geranylgeranyl pyrophosphate, 4 microg recombinant Arabidopsis thaliana RAB-A2a protein, 32°C, 40 min
-
-
?
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
geranylgeranyl diphosphate + Rab
S-geranylgeranyl-Rab + diphosphate
show the reaction diagram
-
His6- and gluthathione S-transferase-tagged Rab proteins such as canine Rab1a, human Rab27a, Rab5a, Rab18, Rab6a, Rab13, and mouse Rab23
-
-
?
geranylgeranyl diphosphate + Rab protein
S-geranylgeranyl-Rab protein + diphosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2-[(1-geranylgeranyl)-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl)bis(phosphonate)
-
compound is able to induce cytotoxicity in human myeloma cells, IC50 value 1 mM
(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,5S)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylic acid
-
slight inhibition of RabGGTase at concentrations above 0.01 mM
2-(3-pyridinyl)-1-ethylidene-1,1-phosphonocarboxylic acid
-
causes rapid accumulation of unprenylated Rabs within the cytosol of osteoclasts and macrophages due to specific inhibition of Rab GGTase
2-(3-pyridinyl)-1-hydroxyethylidene-1,1-bisphosphonic acid
-
causes rapid accumulation of unprenylated Rabs within the cytosol of osteoclasts and macrophages due to specific inhibition of Rab GGTase
2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid
-
causes rapid accumulation of unprenylated Rabs within the cytosol of osteoclasts and macrophages due to specific inhibition of Rab GGTase
2-bromo-3-(3-pyridinyl)-2-phosphonopropionic acid
-
-
2-chloro-3-(3-pyridinyl)-2-phosphonopropionic acid
-
-
2-fluoro-3-(3-pyridinyl)-2-phosphonopropionic acid
-
-
2-hydroxy-2-phosphono-3-pyridin-3-yl-propionic acid
-
3-PEHPC, weak inhibitor, 100% activity remain with concentrations up to 1 microM inhibitor and substrate Rab1a, with 10 microM inhibitor about 60% activity remain, with 100 microM and more inhibitor the activity falls to 30% and below
2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid
-
(+)-3-IPEHPC, the (+)-enantiomer is selective towards the enzyme and more potent than the (-)-enantiomer, mixed type inhibitor with respect to geranylgeranyl diphosphate, uncompetitive inhibitor with respect to Rab substrate, 25fold more potent than 2-hydroxy-2-phosphono-3-pyridin-3-yl-propionic acid, with 1 microM inhibitor activity falls to about 50%, with 10 microM inhibitor and more activity falls below 20%
2-PEPC
-
i.e.3-PEPC, protein geranylgeranyltransferase-II is the major pharmacological target of the inhibitor
3-(1-methylpyridin-1-ium-3-yl)-2-phosphonopropanoate
-
i.e.NE1048 , protein geranylgeranyltransferase-II is the major pharmacological target of the inhibitor
3-(3-pyridinyl)-2-phosphonopropionic acid
-
-
3-PEHPC
-
i.e.3-PEHPC, protein geranylgeranyltransferase-II is the major pharmacological target of the inhibitor
3-PEPC
-
i.e.2-PEPC, protein geranylgeranyltransferase-II is the major pharmacological target of the inhibitor
3-pyridinyl ethylidene hydroxyl phosphonocarboxylate
-
previously known as NE10790
KCl
-
50% inhibition at 100 mM
methyl N-undecanoyl-L-tyrosyl-L-histidyl-L-tyrosinate
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-([[2-(benzyloxy)benzyl]oxy]carbonyl)-D-histidyl-L-tyrosyl-L-phenylalanine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-([[2-(benzyloxy)benzyl]oxy]carbonyl)-L-histidyl-L-tyrosyl-L-phenylalanine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-butanoyl-L-histidyl-L-phenylalanyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-octanoyl-L-histidyl-L-phenylalanyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-pentadecanoyl-L-histidyl-L-phenylalanyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-undecanoyl-L-histidyl-L-histidyl-N-(4-aminobutyl)-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-undecanoyl-L-histidyl-L-histidyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide), not cytotoxic to COS-7 cells, fluorescence titration reveals competitive inhibition
N-undecanoyl-L-histidyl-L-phenylalanyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide), not cytotoxic to COS-7 cells, fluorescence titration reveals partial competitive inhibition which points to a different binding site
N-undecanoyl-L-histidyl-L-phenylalanyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-undecanoyl-L-tyrosyl-L-histidyl-N-(4-aminobutyl)-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-undecanoyl-L-tyrosyl-L-histidyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide), not cytotoxic to COS-7 cells, fluorescence titration reveals competitive inhibition
N-[(2,5-dimethyl-1,3-oxazol-4-yl)carbonyl]glycyl-L-phenylalanyl-1-trityl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2,5-dimethyl-1,3-oxazol-4-yl)carbonyl]glycyl-L-phenylalanyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]-1-trityl-L-histidylglycyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]-1-trityl-L-histidylglycyl-L-phenylalanine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]-L-histidylglycyl-1-trityl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus), not cytotoxic to COS-7 cells, fluorescence titration reveals competitive inhibition
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]-L-histidylglycyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]glycyl-L-phenylalanyl-1-(tert-butoxycarbonyl)-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]glycyl-L-phenylalanyl-1-benzyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]glycyl-L-phenylalanyl-1-trityl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]glycyl-L-phenylalanyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]histidylglycyl-L-phenylalanine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[(2E)-3-(biphenyl-4-yl)prop-2-enoyl]-D-histidyl-L-tyrosyl-L-tyrosine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-[(2E)-3-[2-[(1Z)-pent-1-en-1-yl]phenyl]prop-2-enoyl]-D-histidyl-L-tyrosyl-D-phenylalanine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-[(benzyloxy)carbonyl]-D-tyrosyl-L-phenylalanyl-L-tyrosine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), fluorescence titration reveals competitive inhibition
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-L-tyrosine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), fluorescence titration reveals competitive inhibition
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-D-tyrosinamide
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-L-tryptophanamide
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), not cytotoxic to COS-7 cells
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-L-tyrosinamide
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), not cytotoxic to COS-7 cells
N-[3-(4-pentylphenyl)propanoyl]-D-histidyl-N-methyl-L-phenylalanyl-L-phenylalanine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-[3-(4-pentylphenyl)propanoyl]-D-tyrosyl-L-tyrosyl-L-phenylalanine
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini)
N-[4-(undecyloxy)benzoyl]-L-histidyl-L-histidyl-N-(4-aminobutyl)-L-histidinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-[4-(undecyloxy)benzoyl]-L-histidyl-L-histidyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-histidinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-[4-(undecyloxy)benzoyl]-L-histidyl-L-tyrosyl-N-[3-(1H-imidazol-1-yl)propyl]-L-phenylalaninamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-[4-(undecyloxy)benzoyl]-L-tyrosyl-L-tyrosyl-N-(4-aminobutyl)-L-tyrosinamide
-
class III inhibitors (comprising a lipophilic N-terminus and an amine or N-heterocycle containing a C-terminal amide)
N-[[2-(pyridin-3-yl)-1,3-thiazol-4-yl]carbonyl]glycyl-L-phenylalanyl-1-trityl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[[2-(pyridin-3-yl)-1,3-thiazol-4-yl]carbonyl]glycyl-L-phenylalanyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[[2-(thiophen-2-yl)-1,3-thiazol-4-yl]carbonyl]glycyl-L-phenylalanyl-1-trityl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
N-[[2-(thiophen-2-yl)-1,3-thiazol-4-yl]carbonyl]glycyl-L-phenylalanyl-L-histidine
-
class II inhibitors (combining a heterocyclic ring system at the N-terminus with a free carboxylate at the C-terminus)
NaCl
-
50% inhibition at 100 mM
NaOAc
-
50% inhibition at 100 mM
NE10790
-
a weak bisphosphonate inhibitor
risedronate
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Insulin
-
promotes the phosphorylation of the alpha subunit of enzyme without an effect on beta subunit, and activation of enzyme, insulin increases the amount of geranylgeranylated Rab3 and Rab4 proteins
-
Nonidet P-40
Rab escort protein
-
RGGT increases the ability of Rab escort protein to extract endogenous prenylated Rabs from membranes in vitro by stabilizing a soluble Rab escort protein-RGGT-geranylgeranylated Rab complex
-
additional information
-
the enzyme is absolutely dependent on the Rab escort protein, REP, cloning and expression of His-tagged REP in Escherichia coli, and purification, overview, recombinant Arabidopsis thaliana REP-6His stimulates Rab geranylgeranylation activity in plant but not yeast cell extracts, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00002 - 0.0016
geranylgeranyl diphosphate
0.0011
Ypt1p
-
pH 7.3, 30°C
-
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.013
Rab protein
Rattus norvegicus
-
pH 7.2, 37°C
-
additional information
additional information
Rattus norvegicus
-
double prenylation the rate for the first prenyl transfer reaction is 0.00026/min, while the second prenyl transfer reaction is 4fold slower
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.005 - 0.03356
2-hydroxy-2-phosphono-3-pyridin-3-yl-propionic acid
0.0011
N-undecanoyl-L-histidyl-L-histidyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
displacement titration
0.0054
N-undecanoyl-L-histidyl-L-phenylalanyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
displacement titration
0.0028
N-undecanoyl-L-tyrosyl-L-histidyl-N-methyl-N-[2-(pyridin-2-yl)ethyl]-L-tyrosinamide
-
displacement titration
0.0053
N-[(2-phenyl-1,3-oxazol-4-yl)carbonyl]-L-histidylglycyl-1-trityl-L-histidine
-
displacement titration
0.0045
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-L-tyrosine
-
9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme; displacement titration
0.0145
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-L-tyrosinamide
-
displacement titration
additional information
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1
(2-[(1-geranylgeranyl)-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl)bis(phosphonate)
Homo sapiens
-
temperature not specified in the publication, pH not specified in the publication
0.007
(2R,3R,4S,5R)-2-(3,4-dichlorophenyl)-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0036
(2R,3R,4S,5R)-2-(4-bromophenyl)-1-[(4-methylphenyl)sulfonyl]-4-(pentylsulfanyl)-5-propylpyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0021
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0045
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-[(4-methoxyphenyl)sulfanyl]-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0048
(2R,3R,4S,5R)-2-(4-bromophenyl)-5-ethyl-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0022
(2R,3R,4S,5R)-2-(4-bromophenyl)-5-hexyl-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0047
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(3-chlorophenyl)-5-(cyclopentylmethyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0031
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(4-chlorophenyl)-1-[(4-chlorophenyl)sulfonyl]-5-(cyclopentylmethyl)pyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.007
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(4-chlorophenyl)-5-(cyclopentylmethyl)-1-(phenylsulfonyl)pyrrolidine-3-carboxylic acid
Rattus norvegicus
-
-
0.0177
2-bromo-3-(3-pyridinyl)-2-phosphonopropionic acid
Rattus norvegicus
-
-
0.0164
2-chloro-3-(3-pyridinyl)-2-phosphonopropionic acid
Rattus norvegicus
-
-
0.0163
2-fluoro-3-(3-pyridinyl)-2-phosphonopropionic acid
Rattus norvegicus
-
-
0.03185 - 0.86
2-hydroxy-2-phosphono-3-pyridin-3-yl-propionic acid
0.0353
3-(3-pyridinyl)-2-phosphonopropionic acid
Rattus norvegicus
-
-
0.0241
3-pyridinyl ethylidene hydroxyl phosphonocarboxylate
Rattus norvegicus
-
-
0.0156
N-([[2-(benzyloxy)benzyl]oxy]carbonyl)-D-histidyl-L-tyrosyl-L-phenylalanine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0193
N-([[2-(benzyloxy)benzyl]oxy]carbonyl)-L-histidyl-L-tyrosyl-L-phenylalanine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0227
N-[(2E)-3-(biphenyl-4-yl)prop-2-enoyl]-D-histidyl-L-tyrosyl-L-tyrosine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0152
N-[(2E)-3-[2-[(1Z)-pent-1-en-1-yl]phenyl]prop-2-enoyl]-D-histidyl-L-tyrosyl-D-phenylalanine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0041
N-[(benzyloxy)carbonyl]-D-tyrosyl-L-phenylalanyl-L-tyrosine
Homo sapiens
-
most potent of the class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0227
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-L-tyrosine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0136
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-D-tyrosinamide
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.0052
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-L-tryptophanamide
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.009
N-[(benzyloxy)carbonyl]-L-histidyl-N-methyl-L-phenylalanyl-N-hydroxy-L-tyrosinamide
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.019
N-[3-(4-pentylphenyl)propanoyl]-D-histidyl-N-methyl-L-phenylalanyl-L-phenylalanine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
0.011
N-[3-(4-pentylphenyl)propanoyl]-D-tyrosyl-L-tyrosyl-L-phenylalanine
Homo sapiens
-
class I inhibitors (compounds possessing a free carboxylic or hydroxamic acid at the C-terminus and lipophilic N-termini), 9 microM (3,7,11-trimethyl-12-(7-nitrobenzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,19-trien-1) diphosphate, 3 microM Rab7, 3 microM Rab escort protein, 400 nM enzyme
additional information
additional information
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
development of a continuous fluorometric assay using a protein fluorescence amplifier, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
adenocarcinoma of colon, significant overexpression of RabGGT-beta compared to normal tissue
Manually annotated by BRENDA team
-
both beta subunit levels are similar in male gametophytes, subunit A1 is expressed in all tissues, subunit A2 is expressed significantly only in pollen
Manually annotated by BRENDA team
-
expression of both alpha- and beta-subunit of enzyme as well as Rab escort protein-1
Manually annotated by BRENDA team
-
large cell lung carcinomas, significant overexpression of RabGGT-beta compared to normal tissue
Manually annotated by BRENDA team
-
significant overexpression of RabGGT-beta and Rab-GGT-alpha compared to normal tissue
Manually annotated by BRENDA team
-
significant overexpression of RabGGT-beta and RabGGT-alpha compared to normal tissue
Manually annotated by BRENDA team
-
expression of both alpha- and beta-subunit of enzyme as well as Rab escort protein-1
Manually annotated by BRENDA team
-
subunit B1 is about 10times more abundant in sporophytes than subunit B2, subunit A1 is expressed in all tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
subcellular localization study, overview
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38000
-
theoretical molecular weight of c-Myc-protein-labelled Rabggtb
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme-inhibitor complex with an engeneered enyzme lacking the LRR- and Ig-domains, complexes are prepared by soaking of co-crystallization, diffraction data collection at -173°C
-
at 2.0 Angstrom resolution, the beta subunit forms an alpha-alpha barrel that contains most of the residues in the active site, the alpha subunit consists of a helical domain, an immunoglobulin-like domain and a leucine-rich repeat domain, the N-terminal alpha subunit binds to the active site in the beta subunit
-
at 2.7 Angstom, crystal structure of REP-1 in complex with farnesyl-loaded enzyme, contact between the two proteins is formed through domain II of REP-1 and the alpha subunit of the enzyme
-
in complex with geranylgeranyl diphosphate, hanging drop vapour diffusion method, with 14% (w/v) PEG 3350, 0.2M CaAc2, 0.1 M HEPES pH 7.2
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
component B
-
fresh plant material is frozen in liquid nitrogen, ground on ice with acid-washed sand in 100 mM Tris buffer, pH 7.8, containing 5 mM EGTA, 5 mM EDTA, 10 mM beta-mercaptoethanol, and 10% glycerol, lysate is centrifuged, dialyzed against 50 mM Tris buffer, pH 7.8, containing 10% glycerol, and 1 mM DTT
-
nickel-Sepharose affinity chromatography
-
recombinant enzyme
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of the beta subunit of enzyme by means of the yeast two-hybrid system
development of a two plasmid expression system in Escherichia coli that achieves large quantities of enzyme
-
expressed in Escherichia coli
-
expressed in Sf9 cells
-
expression in Escherichia coli
-
expression in SF21 cells
-
expression in Sf9 cells with recombinant baculovirus
-
recombinant enzyme produced in baculovirus and Escherichia coli system
-
recombinant enzyme produced in insect cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
Show AA Sequence (109 entries)
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