6Y56

MenT4, nucleotidyltransferase toxin Rv2826c from Mycobacterium tuberculosis H37Rv

Summary for 6Y56

• Entry DOI: 10.2210/pdb6y56/pdb
• Descriptor: Uncharacterized protein (2 entities in total)
• Functional Keywords: nucleotidyltransferase toxin-antitoxin system tuberculosis, toxin
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 1
• Total formula weight: 33007.63

Authors

Usher, B.,Blower, T.R. (deposition date: 2020-02-24, release date: 2020-09-16, Last modification date: 2024-05-15)

Primary citation

Cai, Y.,Usher, B.,Gutierrez, C.,Tolcan, A.,Mansour, M.,Fineran, P.C.,Condon, C.,Neyrolles, O.,Genevaux, P.,Blower, T.R.
A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems.
Sci Adv, 6:eabb6651-eabb6651, 2020

PubMed Abstract: Toxin-antitoxin systems are widespread stress-responsive elements, many of whose functions remain largely unknown. Here, we characterize the four DUF1814-family nucleotidyltransferase-like toxins (MenT) encoded by the human pathogen . Toxin MenT inhibited growth of when not antagonized by its cognate antitoxin, MenA. We solved the structures of toxins MenT and MenT to 1.6 and 1.2 Å resolution, respectively, and identified the biochemical activity and target of MenT. MenT blocked in vitro protein expression and prevented tRNA charging in vivo. MenT added pyrimidines (C or U) to the 3'-CCA acceptor stems of uncharged tRNAs and exhibited strong substrate specificity in vitro, preferentially targeting tRNA from among the 45 . tRNAs. Our study identifies a previously unknown mechanism that expands the range of enzymatic activities used by bacterial toxins, uncovering a new way to block protein synthesis and potentially treat tuberculosis and other infections.

PubMed: 32923609
DOI: 10.1126/sciadv.abb6651

Experimental method

X-RAY DIFFRACTION (1.23 Å)