Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 2.5.1.59 - protein geranylgeranyltransferase type I and Organism(s) Candida albicans and UniProt Accession Q9Y765

for references in articles please use BRENDA:EC2.5.1.59
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
This enzyme, along with protein farnesyltransferase (EC 2.5.1.58) and protein geranylgeranyltransferase type II (EC 2.5.1.60), constitutes the protein prenyltransferase family of enzymes. Catalyses the formation of a thioether linkage between the C-1 atom of the geranylgeranyl group and a cysteine residue fourth from the C-terminus of the protein. These protein acceptors have the C-terminal sequence CA1A2X, where the terminal residue, X, is preferably leucine; serine, methionine, alanine or glutamine makes the protein a substrate for EC 2.5.1.58. The enzymes are relaxed in specificity for A1, but cannot act if A2 is aromatic. Known targets of this enzyme include most gamma-subunits of heterotrimeric G proteins and Ras-related GTPases such as members of the Ras and Rac/Rho families. A zinc metalloenzyme. The Zn2+ is required for peptide, but not for isoprenoid, substrate binding.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Candida albicans
UNIPROT: Q9Y765
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Candida albicans
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
ggtase-i, ggtase i, ggtase, geranylgeranyltransferase i, pggt-i, cdc43, protein geranylgeranyltransferase type i, geranylgeranyltransferase type i, protein geranylgeranyltransferase, geranylgeranyltransferase-i, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
geranylgeranyltransferase-I
-
protein geranylgeranyltransferase type I
-
CAAX geranylgeranyltransferase
-
-
-
-
geranylgeranyl protein transferase type I
-
-
-
-
geranylgeranyltransferase-1
-
-
-
-
geranylgeranyltransferaseI
-
-
-
-
GGTase-I
-
-
-
-
GGTaseI
-
-
-
-
PGGT
-
-
-
-
PGGT-I
-
-
-
-
PGGTaseI
-
-
-
-
protein geranylgeranyltransferase
-
-
-
-
protein geranylgeranyltransferase I
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
geranylgeranyl-diphosphate:protein-cysteine geranyltransferase
This enzyme, along with protein farnesyltransferase (EC 2.5.1.58) and protein geranylgeranyltransferase type II (EC 2.5.1.60), constitutes the protein prenyltransferase family of enzymes. Catalyses the formation of a thioether linkage between the C-1 atom of the geranylgeranyl group and a cysteine residue fourth from the C-terminus of the protein. These protein acceptors have the C-terminal sequence CA1A2X, where the terminal residue, X, is preferably leucine; serine, methionine, alanine or glutamine makes the protein a substrate for EC 2.5.1.58. The enzymes are relaxed in specificity for A1, but cannot act if A2 is aromatic. Known targets of this enzyme include most gamma-subunits of heterotrimeric G proteins and Ras-related GTPases such as members of the Ras and Rac/Rho families. A zinc metalloenzyme. The Zn2+ is required for peptide, but not for isoprenoid, substrate binding.
CAS REGISTRY NUMBER
COMMENTARY hide
135371-29-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate + protein-cysteine
S-geranylgeranyl-protein + diphosphate
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
for maximum reaction rate
Zn2+
activating the cysteine thiolate of the substrate
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-[2-[(Z)-[[4-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazin-1-yl]imino]methyl]phenoxy]-N,N-dimethylmethanamine
i.e L-269289, selective chemical inhibition of GGTase I by L-269289 potentiates echinocandin activity and renders echinocandin-resistant Candida albicans responsive to treatment in vitro and in animal models for disseminated infection
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
deleting beta-subunit CDC43 of geranylgeranyltransferase type I confers hypersensitivity to echinocandins. The membrane localization of Rho is disrupted in the CDC43 mutant, resulting in decreased amounts of glucans in the cell wall, thereby exacerbating the cell wall stress upon caspofungin addition
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
FNTA_CANAX
306
0
36601
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37000
alpha-subunit
45000
beta-subunit
82000
heterodimer of the alpha and beta subunits
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
1 * 37000 + 1 * 45000
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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 -173°C
hanging-drop method, crystal structure of GGTase-I in complex with its cognate lipid substrate, geranylgeranylpyrophosphate
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
PCR-amplification and expression in Escherichia coli
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hast, M.A.; Beese, L.S.
Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate
J. Biol. Chem.
283
31933-31940
2008
Candida albicans (Q9Y765), Candida albicans
Manually annotated by BRENDA team
Sun, Q.; Xiong, K.; Yuan, Y.; Yu, J.; Yang, L.; Shen, C.; Su, C.; Lu, Y.
Inhibiting fungal echinocandin resistance by small-molecule disruption of geranylgeranyltransferase type i activity
Antimicrob. Agents Chemother.
64
e02046-19
2020
[Candida] glabrata, Candida parapsilosis, Candida tropicalis, Candida albicans (Q9Y764), Candida albicans
Manually annotated by BRENDA team