Molecular Modeling and Docking Study of 2-Nitropropane Dioxygenase of Mycobacterium tuberculosis

Am, Abid; Ibrahim, BS; Yadav, Pawan Kumar; Arya, Hemant; Rasool, Anam

doi:10.4172/2090-4924.1000127

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…Furthermore, the 3D verification showed that the predicted model was valid for the further docking process of Rv1250 protein of M. tuberculosis ( Abid et al, 2017 ). Following, results were concluded from the Verify-3D assessment model.…”

Section: Resultsmentioning

confidence: 93%

“…The catalase-peroxidase enzyme (KatG) is used to activate the INH, a pro-drug. Then there is a reaction of resulting active species with NAD+ (Nicotinamide adenine dinucleotide) to develop an INH-NAD adduct, which impedes the enoyl acyl carrier protein reductase (InhA), causing the inhibition of mycolic acid biosynthesis and hence, the mycobacterial cell death ( Kumar & Jena, 2014 ; Abid et al, 2017 ). Mutation in KatG gene, a virulence determinant and activator of prodrug INH, is the chief mechanism of resistance of INH.…”

Section: Introductionmentioning

confidence: 99%

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Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

et al. 2023

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Computational prediction and protein structure modeling have come to the aid of various biological problems in determining the structure of proteins. These technologies have revolutionized the biological world of research, allowing scientists and researchers to gain insights into their biological questions and design experimental research much more efficiently. Pathogenic Mycobacterium spp. is known to stay alive within the macrophages of its host. Mycobacterium tuberculosis is an acid-fast bacterium that is the most common cause of tuberculosis and is considered to be the main cause of resistance of tuberculosis as a leading health issue. The genome of Mycobacterium tuberculosis contains more than 4,000 genes, of which the majority are of unknown function. An attempt has been made to computationally model and dock one of its proteins, Rv1250 (MTV006.22), which is considered as an apparent drug-transporter, integral membrane protein, and member of major facilitator superfamily (MFS). The most widely used techniques, i.e., homology modeling, molecular docking, and molecular dynamics (MD) simulation in the field of structural bioinformatics, have been used in the present work to study the behavior of Rv1250 protein from M. tuberculosis. The structure of unknown TB protein, i.e., Rv1250 was retrived using homology modeling with the help of I-TASSER server. Further, one of the sites responsible for infection was identified and docking was done by using the specific Isoniazid ligand which is an inhibitor of this protein. Finally, the stability of protein model and analysis of stable and static interaction between protein and ligand molecular dynamic simulation was performed at 100 ns The designing of novel Rv1250 enzyme inhibitors is likely achievable with the use of proposed predicted model, which could be helpful in preventing the pathogenesis caused by M. tuberculosis. Finally, the MD simulation was done to evaluate the stability of the ligand for the specific protein.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

et al. 2023

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Peculiarities of nitronate monooxygenases and perspectives for in vivo and in vitro applications

Torres-Guzmán

Padilla-Guerrero

Cervantes-Quintero

et al. 2021

Appl Microbiol Biotechnol

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Understanding the Role of Nitronate Monooxygenases in Virulence of the Human Fungal Pathogen Aspergillus fumigatus

Nguyen

Wacker

Brown

et al. 2022

JoF

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Aspergillus fumigatus is the leading cause of the fungal invasive disease called aspergillosis, which is associated with a high mortality rate that can reach 50% in some groups of immunocompromised individuals. The increasing prevalence of azole-resistant A. fumigatus isolates, both in clinical settings and the environment, highlights the importance of discovering new fungal virulence factors that can potentially become targets for novel antifungals. Nitronate monooxygenases (Nmos) represent potential targets for antifungal compounds as no orthologs of those enzymes are present in humans. Nmos catalyse the denitrification of nitroalkanes, thereby detoxifying these mediators of nitro-oxidative stress, and therefore we tested whether Nmos provide protection for A. fumigatus against host-imposed stresses at sites of infection. The results of inhibition zone assays indicated that Nmo2 and Nmo5 are not essential for the oxidative stress resistance of A. fumigatus in vitro. In addition, the resazurin-based metabolic activity assay revealed that the growth of mutants lacking the nmo2 or nmo5 genes was only slightly reduced in the presence of 0.05 mM peroxynitrite. Nevertheless, both Nmo2 and Nmo5 were shown to contribute to defense against murine bone marrow-derived macrophages, and this was no longer observed when NADPH oxidase, the main generator of reactive oxygen species during infection, was inhibited in macrophages. Furthermore, we revealed that Nnmos promote the virulence of the fungus in the Galleria mellonella model of infection. Both nmo2 and nmo5 knock-out strains were less virulent than the wild-type control as recorded 72 h post-infection. Our results indicate that Nmos play a role in the virulence of A. fumigatus.

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Molecular Modeling and Docking Study of 2-Nitropropane Dioxygenase of Mycobacterium tuberculosis

Cited by 3 publications

References 7 publications

Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

Peculiarities of nitronate monooxygenases and perspectives for in vivo and in vitro applications

Understanding the Role of Nitronate Monooxygenases in Virulence of the Human Fungal Pathogen Aspergillus fumigatus

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