Catalytic Mechanism of a Metalloenzyme: Carbonic Anhydrase

Abstract

Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3- [1]. The zinc ion in CA can be substituted by similar transition metal ions, leading to dramatically different catalytic activity. However, the underlying mechanism is not clearly known. In our study, we studied the intermediate states of four divalent transition-metal ions (Zn2+, Co2+, Ni2+, Cu2+) that induce drastic changes in CA II activity (100%, ~ 50%, ~ 2%, and 0%, respectively) [2]. The results show that the characteristic metal ion coordination geometries directly modulate the catalytic processes and that the metal ions have a long-range (~10 Å) electrostatic effect on restructuring the water network at the active site. Our study provides clear evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties.

[References] 1. Kim CU, Song HJ, Avvaru BS, Gruner SM, Park SY and McKenna R Proc. Natl. Acad. Sci. USA, 113 5257, 2016. 2. Kim JK, Lee C, Lim SW, Adhikari A, Andring JT, McKenna R, Ghim CM and Kim CU Nat. Commun., 11, 4557, 2020.