Restoring catalytic activity to the human carbonic anhydrase (CA) related proteins VIII, X and XI affords isoforms with high catalytic efficiency and susceptibility to anion inhibition.

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Nishimori I, Vullo D, Minakuchi T, Scozzafava A, Capasso C, Supuran CT

Restoring catalytic activity to the human carbonic anhydrase (CA) related proteins VIII, X and XI affords isoforms with high catalytic efficiency and susceptibility to anion inhibition.

Bioorg Med Chem Lett. 2013 Jan 1;23(1):256-60. doi: 10.1016/j.bmcl.2012.10.103. Epub 2012 Nov 9.

PubMed ID

23200251 [ View in PubMed

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Abstract

Mutation of amino acid residues 94, 96 and 119 to histidine(s) in the human carbonic anhydrase (CA, EC 4.2.1.1) related proteins CARP VIII, X and XI restored the zinc binding and catalytic activity for the hydration of CO(2) to bicarbonate. CA VIII, X and XI thus obtained showed high catalytic activity (67.3-92.0% of the activity of hCA II and much higher compared to hCA I) and were inhibited in the milli-micromolar range by inorganic anions, sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid. Among the three new isoforms, hCA X was the most efficient enzyme and also showed the highest affinity for anion inhibitors (K(I)s of 3.6-68 muM for phenylboronic acid, sufamic acid, sulfamide, cyanide and azide). hCA VIII was poorly inhibited by halides, cyanate, nitrate and sulfate (K(I)s of 38.4-65.4 mM), whereas CA XI had a behavior intermediate between that of hCA VIII and X, both regarding the catalytic activity and sensitivity to anion inhibitors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	250	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details