Abstract
The cloning, purification, and initial characterization of the β-carbonic anhydrase (CA, EC 4.2.1.1) from the genome of the opportunistic pathogen Malassezia restricta (MreCA), which a fungus involved in dandruff and seborrheic dermatitis (SD), is reported. MreCA is a protein consisting of 230 amino acid residues and shows high catalytic activity for the hydration of CO2 into bicarbonate and protons, with the following kinetic parameters: kcat of 1.06 × 106 s−1 and kcat/KM of 1.07 × 108 M−1 s−1. It is also sensitive to inhibition by the sulfonamide acetazolamide (KI of 50.7 nM). Phylogenetically, MreCA and other CAs from various Malassezia species seem to be on a different branch, distinct from that of other β-CAs found in fungi, such as Candida spp., Saccharomyces cerevisiae, Aspergillus fumigatus, and Sordaria macrospora, with only Cryptococcus neoformans and Ustilago maydis enzymes clustering near MreCA. The further characterization of this enzyme and the identification of inhibitors that may interfere with its life cycle might constitute new strategies for fighting dandruff and SD.
Highlights
Carbonic anhydrases (CA, EC 4.2.1.1) catalyze the simple but physiologically crucial interconversion of carbon dioxide and water into bicarbonate and protons: CO2 + H2O HCO3− + H+ [1,2,3,4,5]
Malassezia restricta (MreCA) and other CAs from various Malassezia species seem to be on a different branch, distinct from that of other β-CAs found in fungi, such as Candida spp., Saccharomyces cerevisiae, Aspergillus fumigatus, and Sordaria macrospora, with only Cryptococcus neoformans and Ustilago maydis enzymes clustering near MreCA
We decided to investigate the analogous enzyme from MgCA, which should be present in the genome of M. restricta. here, we report on the cloning, purification, and characterization of the β-CA from the pathogenic fungus, M. restricta (MreCA)
Summary
Carbonic anhydrases (CA, EC 4.2.1.1) catalyze the simple but physiologically crucial interconversion of carbon dioxide and water into bicarbonate and protons: CO2 + H2O HCO3− + H+ [1,2,3,4,5] These metalloenzymes are indispensable for maintaining the physiological equilibrium of the dissolved CO2, H2CO3, HCO3−, and CO32−, which are metabolites essential for the biosynthesis and energy metabolism of organisms [5,6,7,8,9]. After considering the significant drug resistance problems with azoles and other antifungals [45,46,47,48,49], MgCA was validated as a possible antifungal target
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