scholarly journals Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding

2006 ◽  
Vol 34 (19) ◽  
pp. 5567-5576 ◽  
Author(s):  
Sugopa Sengupta ◽  
Meera Shah ◽  
Valakunja Nagaraja
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Dna Gyrase ◽  
Glutamate Racemase

scholarly journals The key DNA-binding residues in the C-terminal domain of Mycobacterium tuberculosis DNA gyrase A subunit (GyrA)

2006 ◽  
Vol 34 (19) ◽  
pp. 5650-5659 ◽  
Author(s):  
You-Yi Huang ◽  
Jiao-Yu Deng ◽  
Jing Gu ◽  
Zhi-Ping Zhang ◽  
Anthony Maxwell ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Dna Gyrase ◽  
Terminal Domain ◽  
Gyrase A ◽  
A Subunit ◽  
Binding Residues

scholarly journals The α10 helix of DevR, the Mycobacterium tuberculosis dormancy response regulator, regulates its DNA binding and activity

FEBS Journal ◽  
2016 ◽  
Vol 283 (7) ◽  
pp. 1286-1299 ◽  
Author(s):  
Atul Vashist ◽  
D. Prithvi Raj ◽  
Umesh Datta Gupta ◽  
Rajiv Bhat ◽  
Jaya Sivaswami Tyagi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Response Regulator

Ethambutol targets the glutamate racemase of Mycobacterium tuberculosis—an enzyme involved in peptidoglycan biosynthesis

2018 ◽  
Vol 103 (2) ◽  
pp. 843-851 ◽  
Author(s):  
Alka Pawar ◽  
Prakash Jha ◽  
Chandrika Konwar ◽  
Uma Chaudhry ◽  
Madhu Chopra ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Peptidoglycan Biosynthesis ◽  
Glutamate Racemase

scholarly journals Real-time kinetic studies of Mycobacterium tuberculosis LexA-DNA interaction

2021 ◽  
Author(s):  
Chitral Chatterjee ◽  
Soneya Majumdar ◽  
Sachin Deshpande ◽  
Deepak Pant ◽  
Saravanan Matheshwaran
Keyword(s):  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Kinetic Parameters ◽  
Dna Sequences ◽  
Kinetic Studies ◽  
Dna Interaction ◽  
Damage Repair ◽  
Inducible Genes ◽  
Kinetics Of

Transcriptional repressor, LexA, regulates the “SOS” response, an indispensable bacterial DNA damage repair machinery.  Compared to its E.coli ortholog, LexA from Mycobacterium tuberculosis (Mtb) possesses a unique N-terminal extension of additional 24 amino acids in its DNA binding domain (DBD) and 18 amino acids insertion at its hinge region that connects the DBD to the C-terminal dimerization/autoproteolysis domain. Despite the importance of LexA in “SOS” regulation, Mtb LexA remains poorly characterized and the functional importance of its additional amino acids remained elusive. In addition, the lack of data on kinetic parameters of Mtb LexA-DNA interaction prompted us to perform kinetic analyses of Mtb LexA and its deletion variants using Bio-layer Interferometry (BLI). Mtb LexA is seen to bind to different “SOS” boxes, DNA sequences present in the operator regions of damage-inducible genes, with comparable nanomolar affinity. Deletion of 18 amino acids from the linker region is found to affect DNA binding unlike the deletion of the N-terminal stretch of extra 24 amino acids. The conserved RKG motif has been found to be critical for DNA binding. Overall, this study provides insights into the kinetics of the interaction between Mtb LexA and its target “SOS” boxes. The kinetic parameters obtained for DNA binding of Mtb LexA would be instrumental to clearly understand the mechanism of “SOS” regulation and activation in Mtb.

scholarly journals Modulation of DNA-binding activity of Mycobacterium tuberculosis HspR by chaperones

Microbiology ◽  
2008 ◽  
Vol 154 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Twishasri Das Gupta ◽  
Boudhayan Bandyopadhyay ◽  
Sujoy K. Das Gupta
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Binding Activity ◽  
Dna Binding Activity

scholarly journals Extending the Definition of the GyrB Quinolone Resistance-Determining Region in Mycobacterium tuberculosis DNA Gyrase for Assessing Fluoroquinolone Resistance in M. tuberculosis

2012 ◽  
Vol 56 (4) ◽  
pp. 1990-1996 ◽  
Author(s):  
Alix Pantel ◽  
Stéphanie Petrella ◽  
Nicolas Veziris ◽  
Florence Brossier ◽  
Sylvaine Bastian ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Wild Type ◽  
Content Type ◽  
Highly Active ◽  
Definition Of

ABSTRACTFluoroquinolone (FQ) resistance is emerging inMycobacterium tuberculosis. The main mechanism of FQ resistance is amino acid substitution within the quinolone resistance-determining region (QRDR) of the GyrA subunit of DNA gyrase, the sole FQ target inM. tuberculosis. However, substitutions in GyrB whose implication in FQ resistance is unknown are increasingly being reported. The present study clarified the role of four GyrB substitutions identified inM. tuberculosisclinical strains, two located in the QRDR (D500A and N538T) and two outside the QRDR (T539P and E540V), in FQ resistance. We measured FQ MICs and also DNA gyrase inhibition by FQs in order to unequivocally clarify the role of these mutations in FQ resistance. Wild-type GyrA, wild-type GyrB, and mutant GyrB subunits produced from engineeredgyrBalleles by mutagenesis were overexpressed inEscherichia coli, purified to homogeneity, and used to reconstitute highly active gyrase complexes. MICs and DNA gyrase inhibition were determined for moxifloxacin, gatifloxacin, ofloxacin, levofloxacin, and enoxacin. All these substitutions are clearly implicated in FQ resistance, underlining the presence of a hot spot region housing most of the GyrB substitutions implicated in FQ resistance (residues NTE, 538 to 540). These findings help us to refine the definition of GyrB QRDR, which is extended to positions 500 to 540.

scholarly journals ClpX is Essential and Activated by Single Strand DNA Binding Protein in Mycobacteria

2020 ◽  
Author(s):  
Jemila C. Kester ◽  
Olga Kandror ◽  
Tatos Akopian ◽  
Michael R. Chase ◽  
Junhao Zhu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Replication ◽  
Dna Binding ◽  
Drug Targets ◽  
Atp Hydrolysis ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Cellular Functions ◽  
Mycobacterial Growth ◽  
Dna Maintenance

The ClpP1P2 proteolytic complex is essential in Mycobacterium tuberculosis (Mtb). Proteolysis by ClpP1P2 requires an associated ATPase, either ClpX or ClpC1. Here, we seek to define the unique contributions of the ClpX ATPase to mycobacterial growth. We formally demonstrate that ClpX is essential for mycobacterial growth and to understand its essential functions, we identify ClpX-His-interacting proteins by pulldown and tandem mass spectrometry. We find an unexpected association between ClpX and proteins involved in DNA replication, and confirm a physical association between ClpX and the essential DNA maintenance protein Single-Stranded DNA Binding protein (SSB). Purified SSB is not degraded by ClpXP1P2; instead SSB enhances ATP hydrolysis by ClpX and degradation of the model substrate GFP-SsrA by ClpXP1P2. This activation of ClpX is mediated by the C-terminal tail of SSB that had been implicated in the activation of other ATPases associated with DNA replication. Consistent with the predicted interactions, depletion of clpX transcript perturbs DNA replication. These data reveal that ClpX participates in DNA replication and identify the first activator of ClpX in mycobacteria. IMPORTANCE Tuberculosis, caused by Mycobacterium tuberculosis, imposes a major global health burden, surpassing HIV and malaria in annual deaths. The ClpP1P2 proteolytic complex and its cofactor ClpX are attractive drug targets, but their precise cellular functions are unclear. This work confirms ClpX’s essentiality and describes a novel interaction between ClpX and SSB, a component of the DNA replication machinery. Further, we demonstrate that a loss of ClpX is sufficient to interrupt DNA replication, suggesting the ClpX-SSB complex may play a role in DNA replication in mycobacteria.

scholarly journals Structural characterization of VapB46 antitoxin from Mycobacterium tuberculosis : insights into VapB46– DNA binding

FEBS Journal ◽  
2019 ◽  
Vol 286 (6) ◽  
pp. 1174-1190 ◽  
Author(s):  
Madhurima Roy ◽  
Anirban Kundu ◽  
Anirban Bhunia ◽  
Sujoy Das Gupta ◽  
Soumya De ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Structural Characterization
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