Calcineurin (CaN) is present in all eukaryotic cells, including intracellular trypanosomatid parasites such as Trypanosoma cruzi (Tc) and Leishmania spp. (Lspp). In this study, we performed an in silico analysis of the CaN subunits, comparing them with the human (Hs) and looking their structure, post-translational mechanisms, subcellular distribution, interactors, and secretion potential. The differences in the structure of the domains suggest the existence of regulatory mechanisms and differential activity between these protozoa. Regulatory subunits are partially conserved, showing differences in their Ca²⁺-binding domains and myristoylation potential compared with human CaN. The subcellular distribution reveals that the catalytic subunits TcCaNA1, TcCaNA2, LsppCaNA1, LsppCaNA1_var, and LsppCaNA2 associate preferentially with the plasma membrane compared with the cytoplasmic location of HsCaNAα. For regulatory subunits, HsCaNB-1 and LsppCaNB associate preferentially with the nucleus and cytoplasm, and TcCaNB with chloroplast and cytoplasm. Calpain cleavage sites on CaNA suggest differential processing. CaNA and CaNB of these trypanosomatids have the potential to be secreted and could play a role in remote communication. Therefore, this background can be used to develop new drugs for protozoan pathogens that cause neglected disease.

中文翻译：

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来自致病性专性细胞内锥虫的钙调神经磷酸酶的计算机表征：潜在的新生物学作用

钙调神经磷酸酶 (CaN) 存在于所有真核细胞中，包括细胞内锥虫寄生虫，如克氏锥虫( Tc ) 和利什曼原虫。( L spp)。在这项研究中，我们对 CaN 亚基进行了计算机分析，将它们与人类 ( Hs ) 进行了比较，并观察了它们的结构、翻译后机制、亚细胞分布、相互作用物和分泌潜力。域结构的差异表明这些原生动物之间存在调节机制和差异活性。调节亚基部分保守，显示出它们的 Ca ^2+差异结合域和肉豆蔻酰化潜力与人类 CaN 相比。亚细胞分布表明，与Hs CaNAα的细胞质位置相比，催化亚基Tc CaNA1、Tc CaNA2、L sppCaNA1、L sppCaNA1_var 和L sppCaNA2 优先与质膜结合。对于调节亚基，Hs CaNB-1 和L sppCaNB 优先与细胞核和细胞质结合，而Tc具有叶绿体和细胞质的 CaNB。CaNA 上的钙蛋白酶切割位点表明存在差异处理。这些锥虫的 CaNA 和 CaNB 具有被分泌的潜力，并可能在远程通信中发挥作用。因此，这一背景可用于开发针对引起被忽视疾病的原生动物病原体的新药。