Dash Manoswini, Pande Veena, Sinha Abhinav
Division of Epidemiology and Clinical Research, ICMR-National Institute of Malaria Research, New Delhi, India.
Department of Biotechnology, Bhimtal Campus, Kumaun University, Nainital, Uttarakhand, India.
Gene X. 2019 Nov 12;4:100024. doi: 10.1016/j.gene.2019.100024. eCollection 2019 Dec.
Amidst technical challenges which limit successful culture and genetic manipulation of parasites, we used a computational approach to identify a critical target with evolutionary significance. The putative circumsporozoite protein on chromosome 13 of (puCSP)is distinct from the well-known vaccine candidate CSP. The aim of this study was to understand the role of puCSP and its relatedness to the well-known CSP. The study revealed puCSP as a membrane bound E3 ubiquitin ligase involved in ubiquitination. It has a species-specific tetra-peptide unit which is differentially repeated in various strains. The puCSP is different from CSP in terms of stage-specific expression and function. Since E3 ubiquitin ligases are known antimalarial drug targets targeting the proteasome pathway, puCSP, with evolutionary connotation and a key role in orchestrating protein degradation in , can be explored as a potential drug target.
在限制寄生虫成功培养和基因操作的技术挑战中,我们采用了一种计算方法来识别具有进化意义的关键靶点。(puCSP)13号染色体上的推定环子孢子蛋白与著名的疫苗候选物CSP不同。本研究的目的是了解puCSP的作用及其与著名的CSP的相关性。该研究揭示puCSP是一种参与泛素化的膜结合E3泛素连接酶。它有一个物种特异性的四肽单元,在不同菌株中差异重复。puCSP在阶段特异性表达和功能方面与CSP不同。由于E3泛素连接酶是已知的靶向蛋白酶体途径的抗疟药物靶点,具有进化内涵且在疟原虫蛋白质降解调控中起关键作用的puCSP可作为潜在的药物靶点进行探索。