6UX1

Carbonic Anhydrase II Complexed with Salicylic Acid

6UX1 の概要

• エントリーDOI: 10.2210/pdb6ux1/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: aspirin salicylic acid, esterase, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30121.19

構造登録者

Andring, J.T.,Combs, J.E.,McKenna, R. (登録日: 2019-11-06, 公開日: 2020-04-22, 最終更新日: 2023-10-11)

主引用文献

Andring, J.,Combs, J.,McKenna, R.
Aspirin: A Suicide Inhibitor of Carbonic Anhydrase II.
Biomolecules, 10:-, 2020

PubMed Abstract: Carbonic anhydrase II (CAII) is a metalloenzyme that catalyzes the reversible hydration/dehydration of CO/HCO. 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.

PubMed: 32244293
DOI: 10.3390/biom10040527

実験手法

X-RAY DIFFRACTION (1.36 Å)