Macromolecular structure and interaction studies of SigF and Usfx in<i>Mycobacterium tuberculosis</i>

Mustyala, Kiran Kumar; Malkhed, Vasavi; Potlapally, Sarita Rajender; Chittireddy, Venkataramana Reddy; Vuruputuri, Uma

doi:10.3109/10799893.2013.868903

Cited by 8 publications

(7 citation statements)

References 62 publications

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“…In the process, the grid box is generated with 75 · 75 · 75 Å 3 around the active site amino acids which were considered from an earlier study [13]. In the ligand preparation process using the epic program, 5 stereo isomers from 32 structures Tables 1 and 2.…”

Section: Virtual Screeningmentioning

confidence: 99%

“…The structure of SigF was considered from an earlier work [13]. The SigF structure was energy minimized using the protein preparation wizard in Maestro 9.0.111 (Maestro v 9.0.111 Schrodinger LLC, New York, NY) applying OPLS 2001 (optimized potential for liquid simulations 2001) force field with default parameters [14].…”

Section: Virtual Screeningmentioning

confidence: 99%

“…The Virtual screening work flow of Schrodinger involves three consecutive steps: (a) receptor grid generation; (b) ligand preparation; and (c) Glide ligand docking [15]. The grid was generated using the Gridgen module of Schrodinger Suite at the active site amino acid residues [13,16]. The Sigma lifechem small molecule database was considered and retrieved in Sdf file format.…”

Section: Virtual Screeningmentioning

confidence: 99%

“…Production and hosting by Elsevier Ltd. All rights reserved. physiological stress conditions [12,13]. In the present work the in silico screening has been taken up to identify small molecules, which can act as antagonists for the SigF protein.…”

Section: Introductionmentioning

confidence: 99%

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Virtual screening studies to identify novel inhibitors for Sigma F protein of Mycobacterium tuberculosis

Mustyala

Malkhed

Chittireddy

et al. 2015

International Journal of Mycobacteriology

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Tuberculosis (TB) is one of the oldest threats to public health. TB is caused by the pathogen Mycobacterium tuberculosis (MTB). The Sigma factors are essential for the survival of MTB. The Sigma factor Sigma F (SigF) regulates genes expression under stress conditions. The SigF binds to RNA polymerase and forms a holoenzyme, which initiates the transcription of various genes. The Usfx, an anti-SigF protein, binds to SigF and alters the transcription initiation and gene expression. In the present work, virtual screening studies are taken up to identify the interactions between SigF and small molecular inhibitors which can inhibit the formation of holoenzyme. The studies reveal that ARG 104 and ARG 224 amino acid residues of SigF protein are forming important binding interactions with the ligands. The in silico ADME properties for the ligand data set are calculated to check the druggability of the molecules.

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Section: Virtual Screeningmentioning

confidence: 99%

Section: Virtual Screeningmentioning

confidence: 99%

Section: Virtual Screeningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Virtual screening studies to identify novel inhibitors for Sigma F protein of Mycobacterium tuberculosis

Mustyala

Malkhed

Chittireddy

et al. 2015

International Journal of Mycobacteriology

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“…Some critical protein-protein complexes of M. tuberculosis have been solved [96][97][98][99]. In addition, advances in structure modeling and protein-protein docking technologies can help predict and analyze protein interaction complexes [100].…”

Section: From Protein Interactions To Antimicrobial Drug Targetsmentioning

confidence: 99%

Improved understanding of pathogenesis from protein interactions inMycobacteriumtuberculosis

Cui

He²

2014

Expert Review of Proteomics

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Comprehensive mapping and analysis of protein-protein interactions provide not only systematic approaches for dissecting the infection and survival mechanisms of pathogens but also clues for discovering new antibacterial drug targets. Protein interaction data on Mycobacterium tuberculosis have rapidly accumulated over the past several years. This review summarizes the current progress of protein interaction studies on M. tuberculosis, the causative agent of tuberculosis. These efforts improve our knowledge on the stress response, signaling regulation, protein secretion and drug resistance of the bacteria. M. tuberculosis-host protein interaction studies, although still limited, have recently opened a new door for investigating the pathogenesis of the bacteria. Finally, this review discusses the importance of protein interaction data on identifying and screening new anti-tuberculosis targets and drugs, respectively.KEYWORDS: drug targets • Mycobacterium tuberculosis • pathogen-host interaction • protein-protein interaction • stress response Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is one of the most devastating human pathogens. In 2011, there were an estimated 8.7 million new cases of TB and 1.4 million people died from TB [1]. Sophisticated regulations allow M. tuberculosis to counter host-exerted harmful environments, interfere with host signaling pathways, evade immune clearance, survive and replicate in the host. Intracellular protein-protein interactions serve important functions in many complex cellular activities, such as stress response, cell signaling, transcriptional regulation, cell division, cell wall synthesis and protein secretion. In addition, interspecies pathogen-host protein interactions help the pathogen to interfere with host pathways and then evade host immune killing. Analyzing the human protein interactions involved in M. tuberculosis infection provides insights into the infection process. All these kinds of protein interaction data provide a basis for us to understand the molecular mechanisms of M. tuberculosis pathogenesis as well as clues for anti-TB drug design (FIGURE 1). In 1998, Cole et al. sequenced the complete genome of M. tuberculosis and found that this pathogen encodes approximately 4000 genes [2]. Since then, many studies have analyzed the interactions of these genes by using computational and highthroughput experimental technologies.Protein interaction data resource of M. tuberculosis Protein-protein interactions include physical interactions and functional interactions, in which physical interactions refer to the direct binding of two proteins and functional interactions mean these proteins are of functional relevance, for example, they are components of a same cell pathway. Unless specified otherwise, protein interactions in this review mean physical interactions. Obtaining protein-protein interaction data is important to elucidate the functions and mechanisms of this interaction in different cellular processes. The recent advances in the computa...

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Structural insights ofMycobacteriumGTPase-Obg and anti-sigma-F factor Usfx interaction

et al. 2017

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An essential protein for bacterial growth, GTPase-Obg (Obg), is known to play an unknown but crucial role in stress response as its expression increases in Mycobacterium under stress conditions. It is well reported that Obg interacts with anti-sigma-F factor Usfx; however, a detailed analysis and structural characterization of their physical interaction remain undone. In view of above-mentioned points, this study was conceptualized for performing binding analysis and structural characterization of Obg-Usfx interaction. The binding studies were performed by surface plasmon resonance, while in silico docking analysis was done to identify crucial residues responsible for Obg-Usfx interaction. Surface plasmon resonance results clearly suggest that N-terminal and G domains of Obg mainly contribute to Usfx binding. Also, binding constants display strong affinity that was further evident by intermolecular hydrogen bonds and hydrophobic interactions in the predicted complex. Strong interaction between Obg and Usfx supports the view that Obg plays an important role in stress response, essentially required for Mycobacterium survival. As concluded by various studies that Obg is crucial for Mycobacterium survival under stress, this structural information may help us in designing novel and potential inhibitors against resistant Mycobacterium strains.

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Macromolecular structure and interaction studies of SigF and Usfx inMycobacterium tuberculosis

Cited by 8 publications

References 62 publications

Virtual screening studies to identify novel inhibitors for Sigma F protein of Mycobacterium tuberculosis

Virtual screening studies to identify novel inhibitors for Sigma F protein of Mycobacterium tuberculosis

Improved understanding of pathogenesis from protein interactions inMycobacteriumtuberculosis

Structural insights ofMycobacteriumGTPase-Obg and anti-sigma-F factor Usfx interaction

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