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Literature summary extracted from

  • Selvig, K.; Ballou, E.R.; Nichols, C.B.; Alspaugh, J.A.
    Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence (2013), Eukaryot. Cell, 12, 1462-1471.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.5.1.59 gene cdc43, encoding the Ggtase-I beta-subunit, DNA and amino acid sequence determination and analysis, recombinant expression of wild-ype and mutant enzymes Cryptococcus neoformans

Protein Variants

EC Number Protein Variants Comment Organism
2.5.1.59 additional information the cdc43DELTA mutant is created by replacing the entire open reading frame in H99 strain with the dominant nourseothricin (NAT) resistance gene. The cdc43DELTA mutant has a growth defect at 37°C and 39°C. The CDC43 locus is completely deleted in several isolates. The morphology of the cdc43dELTA mutant is indistinguishable from that of the wild-type when grown at 30°C. Both the temperature sensitivity and the morphological defects of the cdc43DELTA mutant are completely rescued by the reintroduction of the wild-type CDC43 allele in the cdc43DELTA CDC43 complemented strain Cryptococcus neoformans

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.59 manumycin A the cdc43DELTA mutant is 2fold more susceptible to this farnesyltransferase inhibitor than the wild-type Cryptococcus neoformans
2.5.1.59 tipifarnib the cdc43DELTA mutant is 4fold more susceptible to this farnesyltransferase inhibitor than the wild-type Cryptococcus neoformans

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.59 geranylgeranyl diphosphate + Cdc42-cysteine Cryptococcus neoformans
-
 S-geranylgeranyl-Cdc42 + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Cdc420-cysteine Cryptococcus neoformans
-
 S-geranylgeranyl-Cdc420 + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + protein-cysteine Cryptococcus neoformans
-
 S-geranylgeranyl-protein + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho10-cysteine Cryptococcus neoformans
-
 S-geranylgeranyl-Rho10 + diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.59 Cryptococcus neoformans J9VNV2 Ggtase-I beta-subunit; diverse strains, gene Cdc43
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.59 geranylgeranyl diphosphate + Cdc42-cysteine
-
 Cryptococcus neoformans S-geranylgeranyl-Cdc42 + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Cdc420-cysteine
-
 Cryptococcus neoformans S-geranylgeranyl-Cdc420 + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + protein-cysteine
-
 Cryptococcus neoformans S-geranylgeranyl-protein + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho10-cysteine
-
 Cryptococcus neoformans S-geranylgeranyl-Rho10 + diphosphate
-
 ?
2.5.1.59 geranylgeranyl diphosphate + Rho10-cysteine while Rho10 has benn previously predicted to lack a CaaX motif, analysis of the Rho10 transcript sequence using RNA sequencing data reveals that one splice site is misannotated, the corrected sequence contains a CLIL C-terminal motif Cryptococcus neoformans S-geranylgeranyl-Rho10 + diphosphate
-
 ?
2.5.1.59 additional information the enzyme has a restricted substrate specificity. Ggtase-I substrates often contain CaaL motifs, overview. Of the three Rho paralogues, only GFP-Rho10 localizes to cellular membranes in wild-type cells. This membrane localization is slightly disrupted in the cdc43DELTA mutant, indicating that the Rho10 protein is likely a Ggtase-I substrate Cryptococcus neoformans ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.59 CaaX prenyltransferase
-
 Cryptococcus neoformans
2.5.1.59 CDC43
-
 Cryptococcus neoformans
2.5.1.59 geranylgeranyltransferase-I
-
 Cryptococcus neoformans
2.5.1.59 Ggtase-1
-
 Cryptococcus neoformans

General Information

EC Number General Information Comment Organism
2.5.1.59 malfunction the related Rac and Ras proteins are not mislocalized in the cdc43DELTA mutant even though they contain similar CaaL motifs, the membrane localization of each of these GTPases is dependent on the prenylation of the CaaX cysteine. The cdc43DELTA mutant has a growth defect at 37°C and 39°C. The cdc43dELTA mutant does not exhibit cell wall defects. The cdc43DELTA mutant is more susceptible to farnesyltransferase inhibitors Cryptococcus neoformans
2.5.1.59 physiological function Cryptococcus neoformans geranylgeranyltransferase-I is involved in high-temperature growth and morphogenesis. The enzyme belongs to the CaaX prenyltransferases (where CaaX indicates a cysteine followed by two aliphatic amino acids and a variable amino acid) that direct the subcellular localization of a large group of proteins by catalyzing the attachment of hydrophobic isoprenoid moieties onto C-terminal CaaX motifs, thus facilitating membrane association. The enzyme-mediated activity is not essential, but is important for thermotolerance, morphogenesis, and virulence. Ggtase-I function is required for full membrane localization of Rho10 and the two Cdc42 paralogues (Cdc42 and Cdc420). Ggtase-I activity are required for full growth in association with macrophages Cryptococcus neoformans