Cloning, expression, post-translational modifications and inhibition studies on the latest mammalian carbonic anhydrase isoform, CA XV

Mika Hilvo, Anna Maria Salzano, Alessio Innocenti, Markku S. Kulomaa, Andrea Scozzafava, Andrea Scaloni, Seppo Parkkila, Claudiu T. Supuran

Research output: Contribution to journalArticleScientificpeer-review

24 Citations (Scopus)

Abstract

We have cloned and purified to homogeneity the latest member of the mammalian α-carbonic anhydrase (CA, EC 4.2.1.1) family, the mouse CA XV (mCA XV) protein. An investigation on the post-translational modifications of the enzyme has also been performed. The enzyme shows a moderate catalytic activity for the physiologic reaction, similarly to the physiologically relevant isoforms CA I, IV, VI, XII, and XIV, and it is susceptible to inhibition by sulfonamides and sulfamates. Best mCA XV inhibitors were celecoxib, sulfanilyl-sulfonamides, methazolamide, ethoxzolamide, dorzolamide, brinzolamide, and sulthiame, with KIs in the range of 45−65 nM. Due to the presence of this enzyme in rather high amounts in the rodent kidneys, the contribution of this isoform to the overall drug response should be taken into account when animal models are used to investigate CA inhibitors.
Original languageEnglish
Pages (from-to)646-654
JournalJournal of Medicinal Chemistry
Volume52
Issue number3
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

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