Sulfonamide Inhibition Studies of the β-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete Sordaria macrospora

  • Molecules. 2020 Feb 25;25(5):1036. doi: 10.3390/molecules25051036.
Daniela Vullo  1 ,  Ronny Lehneck  2 ,  William A Donald  3 ,  Stefanie Pöggeler  2 ,  Claudiu T Supuran  3  4
Affiliations
  • 1. Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze, 50019 Sesto Fiorentino (Florence), Italy.
  • 2. Institute of Microbiology and Genetics, Department of Genetics of Eukaryotic Microorganisms, Georg-August-University, 37077 Gottingen, Germany.
  • 3. University of New South Wales, School of Chemistry, Sydney, NSW 2052, Australia.
  • 4. Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze, 50019 Sesto Fiorentino (Florence), Italy.
PMID: 32106611 DOI: 10.3390/molecules25051036
Abstract

A new β-class Carbonic Anhydrase was cloned and purified from the filamentous ascomycete Sordaria macrospora, CAS3. This enzyme has a higher catalytic activity compared to the Other two such Enzymes from this fungus, CAS1 and CAS2, which were reported earlier, with the following kinetic parameters: kcat of (7.9 ± 0.2) × 105 s-1, and kcat/Km of (9.5 ± 0.12) × 107 M-1∙s-1. An inhibition study with a panel of sulfonamides and one sulfamate was also performed. The most effective CAS3 inhibitors were benzolamide, brinzolamide, dichlorophnamide, methazolamide, acetazolamide, ethoxzolamide, sulfanilamide, methanilamide, and benzene-1,3-disulfonamide, with KIs in the range of 54-95 nM. CAS3 generally shows a higher affinity for this class of inhibitors compared to CAS1 and CAS2. As S. macrospora is a model organism for the study of fruiting body development in fungi, these data may be useful for developing Antifungal compounds based on CA inhibition.

Keywords
Sordaria macrospora; antifungals; carbonic anhydrase; fungus; kinetics; sulfonamide.
Products