Catalytic Inactivation of Human Carbonic Anhydrase I by a Metallopeptide−Sulfonamide Conjugate is Mediated by Oxidation of Active Site Residues

Oxidation of active site residues (His and Trp), following catalytic inactivation of human carbonic anhydrase I by a copper−ATCUN conjugate of sulfanilimide, is evidenced by mass spectrometric analysis of tryptic and chymotryptic digests of the modified CA-I. Accordingly, residue oxidation rather than protein cleavage is the demonstrated mode of inactivation. An apparent second-order rate constant, k 2 ∼ 7600 M -1 min -1, has been determined for catalytic inactivation of CA-I.