Del Prete Sonia, De Luca Viviana, De Simone Giuseppina, Supuran Claudiu T, Capasso Clemente
a Istituto di Bioscienze e Biorisorse, CNR , Napoli , Italy.
b Istituto di Biostrutture e Bioimmagini, CNR , Napoli , Italy , and.
J Enzyme Inhib Med Chem. 2016;31(sup4):54-59. doi: 10.1080/14756366.2016.1217856. Epub 2016 Aug 15.
The antimalarial drugs are of fundamental importance in the control of malaria, especially for the lack of efficient treatments and acquired resistance to the existing drugs. For this reason, there is a continuous work in identifying novel, less toxic and effective chemotherapies as well as new therapeutic targets against the causative agents of malaria. In this context, a superfamily of metalloenzymes named carbonic anhydrases (CAs, EC 4.2.1.1) has aroused a great interest as druggable enzymes to limit the development of Plasmodium falciparum gametocytes. CAs catalyze a common reaction in all life domains, the carbon dioxide hydration to bicarbonate and protons (CO + HO ⇔ HCO + H). P. falciparum synthesizes pyrimidines de novo starting from HCO, which is generated from CO through the action of the η-CA identified in the genome of the protozoan. Here, we propose a procedure for the preparation of a wider portion of the protozoan η-CA, named PfCAdom (358 amino acid residues), with respect to the truncated form prepared by Krungkrai et al. (PfCA1, 235 amino acid residues). The results evidenced that the recombinant PfCAdom, produced as a His-tag fusion protein, was 2.7 times more active with respect the truncated form PfCA1.
抗疟药物在疟疾控制中至关重要，尤其是鉴于缺乏有效的治疗方法以及疟原虫对现有药物产生了耐药性。因此，人们一直在持续努力寻找新型、毒性较低且有效的化疗药物以及针对疟疾病原体的新治疗靶点。在此背景下，一类名为碳酸酐酶（CAs，EC 4.2.1.1）的金属酶超家族作为可成药酶引起了极大关注，有望限制恶性疟原虫配子体的发育。碳酸酐酶在所有生命领域催化一个共同反应，即二氧化碳水合形成碳酸氢根和质子（CO₂ + H₂O ⇔ HCO₃⁻ + H⁺）。恶性疟原虫从HCO₃⁻开始从头合成嘧啶，而HCO₃⁻是通过原生动物基因组中鉴定出的η - CA的作用由CO₂产生的。在此，我们提出了一种制备原生动物η - CA更大部分的方法，命名为PfCAdom（358个氨基酸残基），相较于Krungkrai等人制备的截短形式（PfCA1，235个氨基酸残基）。结果表明，作为His标签融合蛋白产生的重组PfCAdom的活性是截短形式PfCA1的2.7倍。
