Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Biomolecules. 2020 Mar 31;10(4):527. doi: 10.3390/biom10040527.
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.
碳酸酐酶 II（CAII）是一种金属酶，可催化 CO/HCO 的可逆水合/脱水。此外，CAII还具有其他催化反应，包括酯酶活性。阿司匹林（乙酰水杨酸）是一种日常的非处方药，具有酯基和羧酸部分。最近，具有羧酸基团的化合物已被证明可以抑制 CAII。因此，我们假设阿司匹林可以作为酯酶活性的底物，产物水杨酸（SA）是 CAII 的抑制剂。在这里，我们展示了 CAII 与 SA 的复合物的晶体结构，SA 是预先用阿司匹林浸泡过的 CAII 晶体的产物，分辨率为 1.35Å。此外，我们提供了动力学数据来支持 CAII 将阿司匹林转化为其去乙酰化形式 SA 的观察结果。该数据还可以解释阿司匹林半衰期短的原因，因为 CAII 在血液中如此丰富，并且阿司匹林可以作为 CAII 的自杀抑制剂。
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