Document Report Card

ID: ALA1143395

Journal: J Med Chem

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

Authors: Hilvo M, Salzano AM, Innocenti A, Kulomaa MS, Scozzafava A, Scaloni A, Parkkila S, Supuran CT.

Abstract: We have cloned and purified to homogeneity the latest member of the mammalian alpha-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 K(I)s 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.

CiteXplore: 19193158

DOI: 10.1021/jm801267c