7WNR

Data-driven HADDOCK model of mycobacterial nMazE6-operator DNA complex

Summary for 7WNR

• Entry DOI: 10.2210/pdb7wnr/pdb
• Related: 7WJ0
• Descriptor: DNA (5'-D(P*CP*CP*GP*GP*TP*TP*AP*TP*AP*CP*TP*AP*TP*CP*TP*GP*TP*A)-3'), DNA (5'-D(P*TP*AP*CP*AP*GP*AP*TP*AP*GP*TP*AP*TP*AP*AP*CP*CP*GP*G)-3'), Antitoxin MazE6 (3 entities in total)
• Functional Keywords: haddock model, mycobacterial ta system, mazef6, maze6-dna complex, antitoxin, antitoxin-dna complex, antitoxin/dna
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 4
• Total formula weight: 22715.26

Authors

Kumari, K.,Sarma, S.P. (deposition date: 2022-01-19, release date: 2022-10-12, Last modification date: 2024-05-15)

Primary citation

Kumari, K.,Sarma, S.P.
Structural and mutational analysis of MazE6-operator DNA complex provide insights into autoregulation of toxin-antitoxin systems.
Commun Biol, 5:963-963, 2022

PubMed Abstract: Of the 10 paralogs of MazEF Toxin-Antitoxin system in Mycobacterium tuberculosis, MazEF6 plays an important role in multidrug tolerance, virulence, stress adaptation and Non Replicative Persistant (NRP) state establishment. The solution structures of the DNA binding domain of MazE6 and of its complex with the cognate operator DNA show that transcriptional regulation occurs by binding of MazE6 to an 18 bp operator sequence bearing the TANNNT motif (-10 region). Kinetics and thermodynamics of association, as determined by NMR and ITC, indicate that the nMazE6-DNA complex is of high affinity. Residues in N-terminal region of MazE6 that are key for its homodimerization, DNA binding specificity, and the base pairs in the operator DNA essential for the protein-DNA interaction, have been identified. It provides a basis for design of chemotherapeutic agents that will act via disruption of TA autoregulation, leading to cell death.

PubMed: 36109664
DOI: 10.1038/s42003-022-03933-5

Experimental method

SOLUTION NMR