X-ray crystallographic studies of mammalian carbonic anhydrase isozymes.

Abstract

The year 1997 marked the 25th year of x-ray crystallographic studies of the mammalian carbonic anhydrase (CA) isozymes. These remarkable enzymes catalyze the reversible hydration of carbon dioxide (H2O + CO2 ⇔ HCO– 3 + H+) via a zinc-hydroxide mechanism (Coleman, 1986; Silverman and Lindskog, 1988; Christianson and Fierke, 1996). To date, five of the seven known isozymes have yielded x-ray crystal structures: three cytosolic isozymes, human CAI (Kannan et al., 1984), human CA II ( Liljas et al., 1972; Eriksson et al., 1988; Halansson, 19929, and bovine CA III (Eriksson and Liljas, 1993); a membrane-associated isozyme, human CA IV (Stams et al., 1996); and a mitochondrial isozyme, murine CA V (Boriack-Sjodin et al., 1995). X-ray crystallographic studies of cytosolic isozymes I, II, and III have been previously reviewed by Eriksson and Liljas (1991). In this review, we extend structural comparisons within the CA family to include the membrane-associated isozyme IV and the mitochondrial isozyme V. We note that to date, the structures of two mammalian CA isozymes remain undetermined: CA VI, a secretory protein found in saliva, and CA VII, a cytosolic isozyme found primarily in salivary glands.