Human carbonic anhydrase II (CA II) is a zinc metalloenzyme that catalyzes the reversible interconversion of carbon dioxide (CO2) and water to bicarbonate (HCO3-) and proton (H+). To understand the catalytic mechanism of CA II, intermediate states captured during catalytic activity are essential. In this study, the crystallographic intermediate structures of native CA II (Zn2+–CA II) and four types of metallovariants (apo, Co2+, Ni2+, and Cu2+–CA II) are presented. The intermediate structures of the native CA II and metallovariants show that the metal ion coordination geometry depends on metal ion (tetrahedral for Zn2+, tetrahedral to octahedral conversion for Co2+, octahedral for Ni2+, and trigonal bipyramidal for Cu2+). Further investigation demonstrates that these characteristic metal ion coordination geometries affect substrate/product binding and directly modulate the catalytic activity (100% for Zn2+, ~50% for Co2+, ~2% for Ni2+, and 0% for Cu2+). Through a comparative study on the intermediate states, we suggest how metal substitutions on CA II influence its catalytic activity beyond their primary chemical properties.
Publisher
Association of Asia Pacific Physical Societies (AAPPS)