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Literature summary extracted from

  • Bhakt, P.; Shivarathri, R.; Choudhary, D.K.; Borah, S.; Kaur, R.
    Fluconazole-induced actin cytoskeleton remodeling requires phosphatidylinositol 3-phosphate 5-kinase in the pathogenic yeast Candida glabrata (2018), Mol. Microbiol., 110, 425-443 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.150 gene CgFAB1, quantitative real-time PCR expression analysis, recombinant expression of C-terminally GFP-tagged enzyme [Candida] glabrata

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.150 G1867/1870V site-directed mutagenesis, the Cgfab1DELTA mutant carrying CgFab1G1867/1870V is sensitive to both azole and metal ion stress [Candida] glabrata
2.7.1.150 additional information generation of a deletion strain for the CgFAB1 gene, using the homologous recombination-based strategy. The mutant is sensitive to azoles (fluconazole, clotrimazole and ketoconazole), and cell membrane (SDS) and cell wall (caffeine) stressors. The growth of the Cgfab1DELTA mutant is also slightly impaired in the presence of the oxidative stressor, hydrogen peroxide, and at high temperature. MDR genes are activated in the Cgfab1DELTA mutant upon fluconazole exposure [Candida] glabrata

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.150 vacuolar membrane
-
 [Candida] glabrata 5774
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.150 Mg2+ required [Candida] glabrata

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.150 ATP + 1-phosphatidyl-1D-myo-inositol 3-phosphate [Candida] glabrata
-
 ADP + 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.150 [Candida] glabrata
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.150 ATP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
 [Candida] glabrata ADP + 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.1.150 CgFab1
-
 [Candida] glabrata
2.7.1.150 phosphatidylinositol 3-phosphate 5-kinase
-
 [Candida] glabrata
2.7.1.150 PI3P-5 kinase
-
 [Candida] glabrata

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.1.150 30
-
 assay at [Candida] glabrata

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.150 8
-
 assay at [Candida] glabrata

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.150 ATP
-
 [Candida] glabrata

General Information

EC Number General Information Comment Organism
2.7.1.150 malfunction CgFAB1 disruption impaires vacuole homeostasis and actin organization, and the F-actin stabilizing compound jasplakinolide rescues azole toxicity in cytoskeleton defective-mutants including the Cgfab1DELTA mutant. The actin depolymerization factor CgCof1 binds to multiple lipids including phosphatidylinositol 3,5-bisphosphate. CgCof1 distribution along with the actin filament-capping protein CgCap2 is altered upon both CgFAB1 disruption and fluconazole exposure. Actin polymerization inhibition renders fluconazole fully and partially fungicidal in azole-susceptible and azole-resistant Candida glabrata clinical isolates, respectively, thereby, underscoring the role of fluconazole-effectuated actin remodeling in azole resistance. MDR genes are activated in the Cgfab1DELTA mutant upon fluconazole exposure. Fluconazole-treated wild-type and Cgfab1DELTA cells display a 1.5fold increased efflux of the MDR pump substrate rhodamine 6G [Candida] glabrata
2.7.1.150 additional information Gly867 and Gly1870 are required for the functioning of CgFab1 [Candida] glabrata
2.7.1.150 physiological function enzyme CgFab1 is implicated in azole tolerance through actin network remodeling. CgFab1 is required for vacuole homeostasis. Fluconazole induces actin cytoskeletal depolarization in a CgFab1-dependent manner, in part, through the PI 3,5-bisphosphate [PI(3,5)P2]-binding protein, CgCof1. CgFab1 is involved in response to azole, cell membrane and cell wall stress. Fluconazole-treated wild-type and Cgfab1DELTA cells display a 1.5fold increased efflux of the MDR pump substrate rhodamine 6G [Candida] glabrata