Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-170, Brazil.
Cells. 2020 Oct 2;9(10):2225. doi: 10.3390/cells9102225.
The ENA ATPases (from : the exit of sodium) belonging to the P-type ATPases are structurally very similar to the sarco/endoplasmic reticulum Ca-ATPase (SERCA); they exchange Na for H and, therefore, are also known as Na-ATPases. ENA ATPases are required in alkaline milieu, as in the case for , where other transporters cannot mediate an uphill Na efflux. They are also important for salt tolerance, as described for . During their life cycles, protozoan parasites might encounter a high pH environment, thus allowing consideration of ENA ATPases as possible targets for controlling certain severe parasitic diseases, such as Chagas' Disease. Phylogenetic analysis has now shown that, besides the types IIA, IIB, IIC, and IID P-type ATPases, there exists a 5th subgroup of ATPases classified as ATP4-type ATPases, found in and . In malaria, for example, some drugs targeting PfATP4 destroy Na homeostasis; these drugs, which include spiroindolones, are now in clinical trials. The ENA P-type (IID P-type ATPase) and ATP4-type ATPases have no structural homologue in mammalian cells, appearing only in fungi, plants, and protozoan parasites, e.g., , and . This exclusivity makes Na-ATPase a potential candidate for the biologically-based design of new therapeutic interventions; for this reason, Na-ATPases deserves more attention.
ENA ATPases（来自：钠出口）属于 P 型 ATP 酶，在结构上与肌浆/内质网 Ca-ATP 酶（SERCA）非常相似；它们将 Na 交换为 H，因此也被称为 Na-ATP 酶。ENA ATP 酶在碱性环境中是必需的，例如在 中，其他转运蛋白不能介导 Na 的向上流出。它们对于盐耐受也很重要，如 中所述。在其生命周期中，原生动物寄生虫可能会遇到高 pH 环境，因此可以考虑将 ENA ATP 酶作为控制某些严重寄生虫病（如恰加斯病）的可能靶点。系统发育分析表明，除了 IIA、IIB、IIC 和 IID P 型 ATP 酶外，还存在第 5 组 ATP 酶，被归类为 ATP4 型 ATP 酶，存在于 和 中。例如，在疟疾中，一些针对 PfATP4 的药物破坏了 Na 稳态；这些药物包括螺吲哚酮，目前正在临床试验中。ENA P 型（IID P 型 ATP 酶）和 ATP4 型 ATP 酶在哺乳动物细胞中没有结构同源物，仅在真菌、植物和原生动物寄生虫中存在，例如 、 和 。这种独特性使 Na-ATP 酶成为基于生物学的新型治疗干预措施的潜在候选物；出于这个原因，Na-ATP 酶值得更多关注。
