Computational prediction of the effects of non-synonymous single nucleotide polymorphisms on the GPI-anchor transamidase subunit GPI8p of Plasmodium falciparum
| Autor: | Sanjay Kumar Singh, M. Sudhakara Reddy |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Protein subunit Plasmodium falciparum Single-nucleotide polymorphism Context (language use) Computational biology Biology medicine.disease_cause Biochemistry Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biosynthesis Structural Biology medicine Gene Regulatory Networks Mutation Functional analysis Organic Chemistry biology.organism_classification Computational Mathematics 030104 developmental biology chemistry 030220 oncology & carcinogenesis Biosynthetic process Acyltransferases |
| Zdroj: | Computational biology and chemistry. 92 |
| ISSN: | 1476-928X |
| Popis: | Drug resistance is increasingly evolving in malaria parasites; hence, it is important to discover and establish alternative drug targets. In this context, GPI-anchor transamidase (GPI-T) is a potential drug target primarily of its crucial role in the development and survival of the parasite in the GPI anchor biosynthesis pathway. The present investigation was undertaken to explore the plausible effects of nsSNP on the structure and functions of GPI-T subunit GPI8p of Plasmodium falciparum. The GPI8p (PF3D7_1128700) was analyzed using various sequence-based and structure-based computational tools such as SIFT, PROVEAN, PredictSNP, SNAP2, I-Mutant, MuPro, ConSurf, NetSurfP, MUSTER, COACH server and STRING server. Of the 34 nsSNPs submitted for functional analysis, 18 nsSNPs (R124 L, N143 K, Y145 F, V157I, T195S, K379E, I392 K, I437 T, Y438H, N439D, Y441H, N442D, N448D, N451D, D457A, D457Y, I458 L and N460 K) were predicted to have deleterious effects on the protein GPI8p. Additionally, I-Mutant 2.0 and MuPro both showed a decrease in stability after mutation as a result of these nsSNPs, suggesting the destabilization of protein. ConSurf findings suggest that most of the regions were highly conserved. In addition, COACH server was used to predict the ligand binding sites. It was found that no mutation was present at the predicted ligand binding site. The results of the STRING database showed that the protein GPI8p interacts with those proteins which either involve the biosynthetic process of attaching GPI anchor to protein or GPI anchor. The present study suggested that the GPI8p could be a novel target for anti-malarial drugs, which provides significant details for further experimentation. |
| Databáze: | OpenAIRE |
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