8RR6

MenT3 (aka TglT) toxin (Rv1045) from Mycobacterium tuberculosis H37Rv, non-phosphorylated

8RR6 の概要

• エントリーDOI: 10.2210/pdb8rr6/pdb
• 分子名称: Nucleotidyl transferase AbiEii/AbiGii toxin family protein (2 entities in total)
• 機能のキーワード: nucleotidyltransferase, toxin, phosphorylation, translation
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31898.47

構造登録者

Arrowsmith, T.J.,Blower, T.R. (登録日: 2024-01-22, 公開日: 2024-09-11)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.78 Å)