7DU5
The structure of the M.tb MazF-mt1 toxin in complex with a fragment of cognate antitoxin
Summary for 7DU5
| Entry DOI | 10.2210/pdb7du5/pdb |
| Descriptor | Endoribonuclease MazF9, A fragment of MazE-mt1 (2 entities in total) |
| Functional Keywords | mycobacterium tuberculosis, mazf, cocrystal structure, antibacterial peptide, toxin |
| Biological source | Mycobacterium tuberculosis H37Rv More |
| Total number of polymer chains | 3 |
| Total formula weight | 28467.19 |
| Authors | |
| Primary citation | Chen, R.,Zhou, J.,Xie, W. Mechanistic Insight into the Peptide Binding Modes to Two M. tb MazF Toxins. Toxins, 13:-, 2021 Cited by PubMed Abstract: Tuberculosis (TB) is a contagious disease caused by (). It is regarded as a major health threat all over the world, mainly because of its high mortality and drug-resistant nature. Toxin-antitoxin (TA) systems are modules ubiquitously found in prokaryotic organisms, and the well-studied MazEF systems (MazE means "what is it?" in Hebrew) are implicated in the formation of "persister cells" in the pathogen. Here, we report cocrystal structures of MazF-mt1 and -mt9, two important MazF members responsible for specific mRNA and tRNA cleavages, respectively, in complexes with truncated forms of their cognate antitoxin peptides. These peptides bind to the toxins with comparable affinities to their full-length antitoxins, which would reduce the RNA-cleavage capacities of the toxins in vitro. After structural analysis of the binding modes, we systemically tested the influence of the substitutions of individual residues in the truncated MazE-mt9 peptide on its affinity. This study provides structural insight into the binding modes and the inhibition mechanisms between the MazE/F-mt TA pairs. More importantly, it contributes to the future design of peptide-based antimicrobial agents against TB and potentially relieves the drug-resistance problems by targeting novel proteins. PubMed: 33925254DOI: 10.3390/toxins13050319 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.65 Å) |
Structure validation
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