8RR5

MenT1 toxin (rv0078a) from Mycobacterium tuberculosis H37Rv, phosphorylated at T39

Summary for 8RR5

• Entry DOI: 10.2210/pdb8rr5/pdb
• Descriptor: Nucleotidyl transferase AbiEii/AbiGii toxin family protein (2 entities in total)
• Functional Keywords: nucleotidyltransferase, toxin, phosphorylation, translation
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 1
• Total formula weight: 21589.35

Authors

Arrowsmith, T.J.,Blower, T.R. (deposition date: 2024-01-22, release date: 2024-09-11, Last modification date: 2024-10-16)

Primary citation

Arrowsmith, T.J.,Xu, X.,Xu, S.,Usher, B.,Stokes, P.,Guest, M.,Bronowska, A.K.,Genevaux, P.,Blower, T.R.
Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins.
Nat Commun, 15:7719-7719, 2024

PubMed Abstract: Nucleotidyltransferases (NTases) control diverse physiological processes, including RNA modification, DNA replication and repair, and antibiotic resistance. The Mycobacterium tuberculosis NTase toxin family, MenT, modifies tRNAs to block translation. MenT toxin activity can be stringently regulated by diverse MenA antitoxins. There has been no unifying mechanism linking antitoxicity across MenT homologues. Here we demonstrate through structural, biochemical, biophysical and computational studies that despite lacking kinase motifs, antitoxin MenA induces auto-phosphorylation of MenT by repositioning the MenT phosphoacceptor T39 active site residue towards bound nucleotide. Finally, we expand this predictive model to explain how unrelated antitoxin MenA is similarly able to induce auto-phosphorylation of cognate toxin MenT. Our study reveals a conserved mechanism for the control of tuberculosis toxins, and demonstrates how active site auto-phosphorylation can regulate the activity of widespread NTases.

PubMed: 39231966
DOI: 10.1038/s41467-024-51934-1

Experimental method

X-RAY DIFFRACTION (2.8 Å)