Characterization, bioinformatic analysis and dithiocarbamate inhibition studies of two new α-carbonic anhydrases, CAH1 and CAH2, from the fruit fly Drosophila melanogaster

Leo Syrjänen (Corresponding Author), Martti E.E. Tolvanen, Mika Hilvo, Daniela Vullo, Fabrizio Carta, Claudiu T. Supuran, Seppo Parkkila

Research output: Contribution to journalArticleScientificpeer-review

10 Citations (Scopus)

Abstract

Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there are no articles on characterization of Drosophila melanogaster α-CAs. Data from invertebrate CA studies may provide opportunities for anti-parasitic drug development because α-CAs are found in many parasite or parasite vector invertebrates. We have expressed and purified D. melanogaster CAH1 and CAH2 as proteins of molecular weights 30 kDa and 28 kDa. CAH1 is cytoplasmic whereas CAH2 is a membrane-attached protein. Both are highly active enzymes for the CO2 hydration reaction, being efficiently inhibited by acetazolamide. CAH2 in the eye of D. melanogaster may provide a new animal model for CA-related eye diseases. A series of dithiocarbamates were also screened as inhibitors of these enzymes, with some representatives showing inhibition in the low nanomolar range.
Original languageEnglish
Pages (from-to)1516-1521
JournalBioorganic & Medicinal Chemistry
Volume21
Issue number6
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Keywords

  • Carbonic anhydrase
  • drosophila melanogaster
  • inhibition
  • phylogenetics

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