title: Cloning, expression, post-translational modifications and inhibition studies on the latest mammalian carbonic anhydrase isoform, CA XV.
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.
authors.affiliation: Institute of Medical Technology, University of Tampere and Tampere University Hospital, Biokatu 6, FI-33520, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Hilvo
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salzano
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Markku S
authors.initials: MS
authors.lastname: Kulomaa
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D051379:Mice; D011499:Protein Processing, Post-Translational
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D002256:Carbonic Anhydrases; C507974:carbonic anhydrase XV, mouse