Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
Bioorg Chem. 2018 Oct;80:94-98. doi: 10.1016/j.bioorg.2018.06.002. Epub 2018 Jun 4.
The first activation study of a η-class carbonic anhydrase (CAs, EC 4.2.1.1) is reported. A panel of 24 natural and non-natural amino acids and amines was used to explore the activation profile of Plasmodium falciparum CA (PfACA). The most effective activators belonged to the amino acid chemotype, with d-Glu, l-Asp, l-/d-Phe and l-/d-DOPA possessing activation constant in the range of 82 nM-0.75 µM, whereas l-/d-His, l-Tyr, 4-amino-l-Phe and l-Gln were slightly less effective (K in the range of 1.00-2.51 µM. The only amine with submicromolar activating properties was 1-(2-aminoethyl-piperazine) with a K of 0.71 µM, whereas histamine, dopamine and serotonin showed K ranging between 7.18 and 9.97 µM. As CA activators have scarcely been investigated for their interaction with protozoan CAs, this study may be relevant for an improved understanding of the role of this enzyme in the life cycle of the malaria producing organisms belonging to the genus Plasmodium.
本文报道了首例 η 类碳酸酐酶（CAs，EC 4.2.1.1）的激活研究。使用了一组 24 种天然和非天然氨基酸和胺来探索恶性疟原虫 CA（PfACA）的激活特性。最有效的激活剂属于氨基酸类化学型，d-Glu、l-Asp、l-/d-Phe 和 l-/d-DOPA 的激活常数在 82nM-0.75µM 范围内，而 l-/d-His、l-Tyr、4-氨基-l-Phe 和 l-Gln 的效果略差（K 在 1.00-2.51µM 范围内。唯一具有亚微摩尔激活特性的胺是 1-（2-氨基乙基-哌嗪），其 K 为 0.71µM，而组氨酸、多巴胺和 5-羟色胺的 K 值在 7.18 和 9.97µM 之间。由于 CA 激活剂在与原生动物 CA 的相互作用方面几乎没有被研究过，因此这项研究可能有助于更好地理解这种酶在疟原虫属的产疟生物生命周期中的作用。
