QM-cluster model study of CO2 hydration mechanisms in metal-substituted human carbonic anhydrase II. (1st March 2023)

• Record Type: Journal Article
• Authors: Summers, Thomas J; DeYonker, Nathan J
• Is Part Of: Electronic structure. Volume 5:Number 1(2023)
• Publication Date: 2023-03-01
• Subjects: carbonic anhydrase -- reaction mechanism -- metal substitution -- computational enzymology; Electronic structure -- Periodicals; 530.411
• DOI: 10.1088/2516-1075/acb02c
• Languages: English
• ISSNs: 2516-1075

Abstract

Abstract: Human carbonic anhydrase (CA) metalloenzymes utilize a Zn 2+ -containing active site to catalyze the interconversion of carbon dioxide to bicarbonate. The Zn 2+ ion may be replaced with other divalent transition metals, though the catalytic efficiency of the enzyme will be reduced. In this work, quantum mechanical cluster models of the active site are used to map the reaction profile for the hydration mechanism of carbon dioxide. The Lipscomb proton transfer and Lindskog rotation mechanisms were examined for the native Zn 2+ -enzyme along with variants where the metal was substituted with Cd 2+, Ni 2+, Fe 2+, and Fe 3+ . The findings highlight the impact the metal coordination geometry has on the reaction profile. The results also suggest Fe 2+, which is the functional metal for a prototypical CA of an anaerobic bacterium, might also be functional for human CA if cultured within an anaerobic environment.