Interaction of the unique competitive inhibitor imidazole with human carbonic anhydrase B.
Imidazole was previously found to be unique among the inhibitors of human carbonic anhydrase B (HCAB) in that it binds competitively with the CO2 substrate (Khalifah, R. G. (1971), J. Biol. Chem. 246, 2561). We report here an aromatic ultraviolet difference spectral study of its interaction with HCAB and compare it with a variety of other inhibitors. Imidazole is found to be unique in that: (1) it generates a different spectrum upon binding that is also much supressed in intensity; (2) its affinity for HCAB is maximal at high pH, being abolished upon its protonation and being independent of active-site ionizations. Imidazole differs from CO2 in that it binds competitively with the anionic inhibitor iodide. The unique properties of imidazole binding are consistent with the recently determined crystal structure of its complex with HCAB showing it to bind as a weak and distant fifth ligand of the essential zinc atom, rather than displacing the solvent molecule in the fourth ligand position (Kannan, K.K., Petef,  M., Fridborg, K., Cid-Dresdner, H., and Lövgren, S. (1977), FEBS Lett 73, 115).
D001667:Binding, Competitive; D002256:Carbonic Anhydrases / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007093:Imidazoles; D007700:Kinetics; D008433:Mathematics; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet
D007093:Imidazoles; D002256:Carbonic Anhydrases