Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Pesquisa em Malária, Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2021 May 31;116:e200584. doi: 10.1590/0074-02760200584. eCollection 2021.
In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.
在本研究中，我们调查了巴西主要疟疾热点地区的两个城市（即茹鲁阿河谷）中恶性疟原虫 metacaspase1（PvMCA1）催化结构域的遗传多样性，观察到所有恶性疟原虫现场分离株与 Sal-1 参考株之间完全的序列同一性。对不同恶性疟原虫基因组序列中 PvMCA1 催化结构域的分析也显示了全球范围内的高度保守性，只有极少数氨基酸取代与假定的组氨酸和半胱氨酸催化残基无关，通过分子建模预测了这些取代与蛋白酶活性位点的关系。PvMCA1 所呈现的遗传保守性可能有助于将其作为间日疟原虫的候选可用药靶。
