1,3-beta-Glucan synthase: a useful target for antifungal drugs.
1,3-beta-glucan synthase, a multisubunit enzyme, is responsible for fungal cell wall construction, division septum deposition, and ascospore wall assembly. The catalytic subunit of this enzyme complex, an integral membrane protein, has been identified both in model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and in pathogenic fungi such as Candida, Aspergillus, Cryptococcus and Pneumocystis species. The catalytic activity of the 1,3-beta-glucan synthase is regulated by a small GTPase of the Ras superfamily, the Rho-GTPase, and protein kinase C (Pkc)-like signaling molecules. It has been shown that the plasma membrane localization of this enzyme is essential for its activity. Interestingly, inhibition of 1,3-beta-glucan synthase activity by anti-fungal drugs of the lipopeptide type triggers a cell cycle feedback mechanism leading to cell cycle arrest. Recent progress in studies of molecular mechanisms of the temporal and spatial regulation of 1,3-beta-glucan synthase is presented. The implication of the cell cycle checkpoint that is activated by the anti-fungal drugs is also discussed.
Liu
J
J
Institute of Molecular Agrobiology, 1 Research Link, National University of Singapore, Singapore 117604, Republic of Singapore. jliu@ima.org.sg
Balasubramanian
M K
MK
D000935:Antifungal Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000032:analysis; D020134:Catalytic Domain; D025141:Drug Resistance, Fungal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005656:Fungal Proteins; D005658:Fungi / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008565:Membrane Proteins; D029702:Schizosaccharomyces pombe Proteins; D013172:Spores, Fungal / Q000502:physiology
D000935:Antifungal Agents; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008565:Membrane Proteins; D029702:Schizosaccharomyces pombe Proteins; C112788:echinocandin-binding protein, 40-kDa, Candida albicans; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase