The catalytic mechanism of mammalian carbonic anhydrases

摘要: The physiological reaction catalyzed by carbonic anhydrase (CA) involves only six atoms at the substrate level: CO2 + H2O ↔ HCO 3 – H+ Despite this simplicity, some aspects of catalytic mechanism have been elusive, and it is not until recently that a rather detailed picture has emerged molecular events taking place in enzymic active site during cycle. These advances are results application combination techniques, such as x-ray crystallography, site-specific mutagenesis, enzyme kinetics computer simulations. Most work concerns cytosolic high-activity isozyme, human CA II (HCA II), but available evidence indicates all CAs animal type (α-CAs) share same general mechanism, usually called zinc-hydroxide (Silverman Lindskog, 1988; Silverman, 1991; Lindskog Liljas, 1993; Liljas et al., 1994; 1997). Thus, believed central step a-CAs between zinc-bound OH– ion yielding coordinated ion, which displaced from metal water molecule. subsequent regeneration transfer molecule to bulk solution. In chapter, we will focus on these they occur HCA II, specific features mechanisms other mammalian isozymes also be discussed.