Active Site Studies on Muscle Carbonic Anhydrase III a

Carbonic anhydrase occurs, in reptiles, birds and mammals, in at least three genetically distinct isozyme forms designated CA I, CA 11, and CA 111. I The CA I11 isozymes, which are abundantly present in red skeletal muscle, possess notably low C02 hydratase and esterase (p-nitrophenyl acetate) a c t i v i t i e ~ ~ , ~ and are remarkably resistant to inhibition by some su l f~namides~ .~ when compared with CA I and CA 11. CA I11 isozymes from rabbit, pig and bovine muscle have also been shown to possess a novel low acid phosphatase activity.* These data tempt speculation that the CA I11 isozymes may have an as yet unknown physiological role other than catalysis of COz hydration. The active site structure of the CA I11 isozymes shows striking differences from those of CA I and CA 11.' Of the five putative active site residues unique to CA I11 and invariant in all CA 111 isozymes examined, two, at positions 67 and 91, are arginine. It has been previously demonstrated that the treatment of bovine and gorilla CA I11 with butanedione results in the activation of the bicarbonate dehydration reaction, whereas the bovine and human CA I and CA I1 isozymes were unaffected by similar t rea t~nent .~ This report is an extension of those studies.