Role of Zinc Ion during Enzyme Catalysis

Abstract

Carbonic anhydrases are mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3. Until now, the role of zinc in carbonic anhydrase II (CA II) has been studied as a Lewis acid, stabilizing a hydroxyl ion in the active site. In this presentation, we show 14 crystallographic structures of apo-CA II (zinc free, no enzymatic activity) and holo-CA II (zinc containing native form) at multiple CO2 (substrate) pressurized conditions to explore the role of the metal on the active site solvent organization. Our results reveal that the zinc ion plays a critical role in the water network replenishment and proton transfer by fine-tuning transient waters during the catalytic cycle. This study provides evidence that the zinc in CA II has a long-range effect beyond the ionization of the zinc-bound water.