NEUROFARBA Department, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, Università degli Studi di Firenze, 50019 Sesto Fiorentino (Florence), Italy.
Centre of Advanced Research in Bionanoconjugates and Biopolymers Department, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iasi, Romania.
Molecules. 2020 May 12;25(10):2269. doi: 10.3390/molecules25102269.
Carbonic anhydrase (CA) is a zinc enzyme that catalyzes the reversible conversion of carbon dioxide to bicarbonate and proton. Currently, CA inhibitors are widely used as antiglaucoma, anticancer, and anti-obesity drugs and for the treatment of neurological disorders. Recently, the potential use of CA inhibitors to fight infections caused by protozoa, fungi, and bacteria has emerged as a new research line. In this article, the X-ray crystal structure of β-CA from was reported. The X-ray crystal structure of this new enzyme was solved at 2.7 Å resolution, revealing a tetrameric type II β-CA with a "closed" active site in which the zinc is tetrahedrally coordinated to Cys46, Asp48, His102, and Cys105. is known to encode at least two CAs, a β-CA, and a γ-CA. These proteins, playing a pivotal role in its life cycle and pathogenicity, offer a novel therapeutic opportunity to obtain antibiotics with a different mechanism of action. Furthermore, the new structure can provide a clear view of the β-CA mechanism of action and the possibility to find selective inhibitors for this class of CAs.
碳酸酐酶（CA）是一种锌酶，可催化二氧化碳可逆转化为碳酸氢根和质子。目前，CA 抑制剂被广泛用作抗青光眼、抗癌和抗肥胖药物，并用于治疗神经紊乱。最近，CA 抑制剂在治疗原生动物、真菌和细菌感染方面的潜在用途已成为一个新的研究方向。本文报道了来自的β-CA 的 X 射线晶体结构。该新酶的 X 射线晶体结构以 2.7Å 的分辨率解决，揭示了一种四聚体 II 型β-CA，其“封闭”活性部位中锌与 Cys46、Asp48、His102 和 Cys105 呈四面配位。已知编码至少两种 CA，一种是β-CA，另一种是γ-CA。这些蛋白质在其生命周期和致病性中发挥着关键作用，为获得具有不同作用机制的抗生素提供了一个新的治疗机会。此外，新结构可以清楚地了解β-CA 的作用机制，并有可能找到针对这类 CA 的选择性抑制剂。
