EXAFS STUDIES OF HUMAN CARBONIC-ANHYDRASE

Human Carbonic Anhydrase (HCA) is a zinc metalloenzyme which catalyzes the hydration of carbon dioxide. It is known to exist in at least nin e distinct isoforms, which have widely different catalytic activities. HCA II is one of the fastest enzymes known. Structural data from X-ra y diffraction is available for HCA I and II only. We have obtained hig h-quality EXAFS data from the zinc K edge for active HCA I, II and III in aqueous solution and analyzed it using restrained refinement with inclusion of multiple-scattering effects. We find the zinc environment to comprise three imidazole rings from histidine residues and one oxy gen atom, presumably from a water molecule. The orientation of the rin gs is well-defined. Despite the variation in catalytic activity betwee n the three forms we find the zinc environment to be essentially ident ical in them all.