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.


Mutation of amino acid residues 94, 96 and 119 to histidine(s) in the human carbonic anhydrase (CA, EC 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 μM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anions / chemistry*
  • Biocatalysis
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / metabolism*
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Alignment


  • Anions
  • Biomarkers, Tumor
  • CA10 protein, human
  • CA11 protein, human
  • CA8 protein, human
  • Carbonic Anhydrase Inhibitors
  • Nerve Tissue Proteins