In silico identification and characterization of a hypothetical protein of Mycobacterium tuberculosis EAI5 as a potential virulent factor

Abstract

Tuberculosis, a life threatening disease caused by different strains of Mycobacterium tuberculosis is creating an alarming condition due to the emergence of increasing multi drug resistance (MDR) trait. In this study, in silico approach was used for the identification of a conserved novel virulent factor in Mycobacterium tuberculosis EAI5 (Accession no.CP006578) which can also act as potential therapeutic target. Systematic comparative search of genes that are common to strain EAI5 and other human pathogenic strains of M. tuberculosis enlisted 408 genes. These were absent in the non-pathogenic Mycobacterium smegmatis MC2155 and in the human genome. Among those genes, only the protein coding hypothetical genes (97 out of 408) and their corresponding products were selected for further exploration. Of these, 11 proteins were found to have notable conserved domains, of which one hypothetical protein (NCBI Acc No. AGQ35418.1) was selected for further in silico exploration which was found to have two functional domains, one having phosphatidylinositol specific phospholipase C (PI-PLC) activity while the other short domain with weak lectin binding activity. As PI-PLC contributes virulence property in some pathogenic bacteria with a broad range of activities, different bioinformatic tools were used to explore its physicochemical and other important properties which indicated its secretary nature. This PI-PLC was previously not reported as drug/vaccine target to the best of our knowledge. Its predicted 3D structure can be explored for development of inhibitor for novel therapeutic strategies against MDR-TB.

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

“…To the best of our knowledge, this protein has not been mentioned as a potential novel therapeutic target in previous research [ 77 , 78 , 121 - 124 ]. Our research presents a new target for the development of efficacious treatments against infections resulting from MDR and XDR Mtb strains.…”

“…Several drug repositioning studies have been conducted on druggable proteins of Mtb, in which multiple drugs were available either for selected proteins of Mtb or homologous proteins of other pathogenic species [ 78 , 121 ]. Two groups utilized subtractive proteomics to screen out promising therapeutic compounds [ 122 , 123 ], and two other groups screened out vaccine targets [ 77 , 124 ]. However, neither group conducted immunoinformatics to design a vaccine, nor did they predict MmpL4 as a potential drug target or vaccine candidate.…”

Functional analysis of conserved hypothetical proteins from the Antarctic yeast, Glaciozyma antarctica PI12

“…The range of sequences considered for selection was limited to those with a length of 500 to 1500 bp. This limitation was imposed due to the tendency of shorter sequences to produce peptides of small size and longer sequences to give rise to proteins with multiple domains, which complicates the characterization procedures (Bertone, 2001;Gupta et al, 2016).…”

Structure to function analysis with antigenic characterization of a hypothetical protein, HPAG1_0576 from Helicobacter pylori HPAG1

“…To investigate the mechanism of a protein that is like Tip- α, it was necessary to establish the structure-function relationship [8]. In this study, the 3D structure of HPAG1_0576 was predicted by homology modeling and later was used for screening and designing new compound leading to the development of novel therapeutic strategy [9]. In addition, primary and secondary sequence/structure analyses, functional annotation, binding site prediction, PPI network generation were also performed.…”