title: Molecular cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Malassezia globosa, a potential antidandruff target.
abstract: A β-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Malassezia globosa has been cloned, characterized, and studied for its inhibition with sulfonamides. This enzyme, designated MG-CA, has significant catalytic activity in the CO(2) hydration reaction and was inhibited by sulfonamides, sulfamates, and sulfamides with K(I) in the nanomolar to micromolar range. Several sulfonamides have also been investigated for the inhibition of growth of M. globosa, M. dermatis, M. pachydermatic, and M. furfur in cultures, whereas a mouse model of dandruff showed that treatment with sulfonamides led to fragmented fungal hyphae, as for the treatment with ketoconazole, a clinically used antifungal agent. These data prompt us to propose MG-CA as a new antidandruff drug target.
authors.affiliation: Union Life Sciences Ltd., 24 Cornhill, London, EC3V 3ND, UK.
authors.forename: Kirsty S
authors.initials: KS
authors.lastname: Hewitson
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Antonio
authors.initials: A
authors.lastname: Mastrolorenzo
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000235:genetics; D003001:Cloning, Molecular; D003881:Dermatomycoses / Q000188:drug therapy / Q000382:microbiology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D008290:Malassezia / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D012536:Scalp Dermatoses / Q000188:drug therapy / Q000382:microbiology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D002257:Carbonic Anhydrase Inhibitors; D005656:Fungal Proteins; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D013449:Sulfonamides; D013451:Sulfonic Acids; D002256:Carbonic Anhydrases