Citation

Andring J, Combs J, McKenna R. Biomolecules 2020; 10(4): e527.

Copyright

(Copyright © 2020, Switzerland Molecular Diversity Preservation International (MDPI) AG)

DOI

10.3390/biom10040527

PMID

32244293

PMCID

PMC7226357

Abstract

Carbonic anhydrase II (CAII) is a metalloenzyme that catalyzes the reversible hydration/dehydration of CO2/HCO3-. In addition, CAII is attributed to other catalytic reactions, including esterase activity. Aspirin (acetyl-salicylic acid), an everyday over-the-counter drug, has both ester and carboxylic acid moieties. Recently, compounds with a carboxylic acid group have been shown to inhibit CAII. Hence, we hypothesized that Aspirin could act as a substrate for esterase activity, and the product salicylic acid (SA), an inhibitor of CAII. Here, we present the crystal structure of CAII in complex with SA, a product of CAII crystals pre-soaked with Aspirin, to 1.35Å resolution. In addition, we provide kinetic data to support the observation that CAII converts Aspirin to its deacetylated form, SA. This data may also explain the short half-life of Aspirin, with CAII so abundant in blood, and that Aspirin could act as a suicide inhibitor of CAII.

Language: en

Keywords

Kinetics; Aspirin; salicylic acid; Enzyme Inhibitors; esterase; carbonic anhydrase; Carbonic Anhydrase II; Catalytic Domain; Models, Molecular; X-ray crystallography