8qnq | pdb_00008qnq

Structure of the toxin-antitoxin NatRT complex from Pseudomonas aeruginosa. NatTE29D mutant

Loading... Status: waiting for Mol* initialization Structural highlights 8qnq is a 6 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.386Å Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9I4U5_PSEAE Publication Abstract from PubMed Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides. While actively growing P. aeruginosa cells compensate for NatT-mediated NAD(+) deficiency by inducing the NAD(+) salvage pathway, NAD depletion generates drug-tolerant persisters under nutrient-limited conditions. Our structural and biochemical analyses propose a model for NatT toxin activation and autoregulation and indicate that NatT activity is subject to powerful metabolic feedback control by the NAD(+) precursor nicotinamide. Based on the identification of natT gain-of-function alleles in patient isolates and on the observation that NatT increases P. aeruginosa virulence, we postulate that NatT modulates pathogen fitness during infections. These findings pave the way for detailed investigations into how a toxin-antitoxin system can promote pathogen persistence by disrupting essential metabolic pathways. Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.,Santi I, Dias Teixeira R, Manfredi P, Hernandez Gonzalez H, Spiess DC, Mas G, Klotz A, Kaczmarczyk A, Zamboni N, Hiller S, Jenal U EMBO J. 2024 Sep 25. doi: 10.1038/s44318-024-00248-5. PMID:39322758 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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