21XG

Multinuclear iron enzymes expand RiPP chemical diversity to enable bacterial oxidative stress defense

This is a non-PDB format compatible entry.

Summary for 21XG

• Entry DOI: 10.2210/pdb21xg/pdb
• Descriptor: DUF2282 domain-containing protein (2 entities in total)
• Functional Keywords: involved in oxidative stress defense, unknown function
• Biological source: Pseudomonas protegens Pf-5
• Total number of polymer chains: 1
• Total formula weight: 7006.82

Authors

He, Y.X.,Feng, H.Z. (deposition date: 2026-01-03, release date: 2026-09-16)

Primary citation

Feng, H.,Xu, H.,Chu, Z.,Li, X.,Hou, J.,Wang, J.,Xu, H.,Cao, H.,Ming, W.,Yang, H.,Lei, X.,He, Y.X.
Multinuclear iron enzymes expand RiPP chemical diversity to enable bacterial oxidative stress defense.
Cell Chem Biol, 2026

PubMed Abstract: RiPP structural complexity is significantly expanded by multinuclear non-heme iron-dependent oxidative enzymes (MNIOs). Here, we characterize pseudoprobactin 1 and 2, two MNIO-modified proteins from Pseudomonas protegens Pf-5. Using MS, NMR, and X-ray crystallography, we show that the PbnBC converts precursor cysteines into 5-thiooxazoles. While the precursors feature an N-terminal signal peptide and an intramolecular disulfide, both are dispensable for catalysis. Instead, residues downstream of the target cysteines are the primary determinants of substrate recognition. Furthermore, PbnB2C2 modifies multiple sites in a strictly ordered, stepwise manner. Functionally, pseudoprobactins coordinate Cu, enhancing bacterial fitness under chlorite-induced oxidative stress. This work establishes 5-thiooxazole as a widespread MNIO-mediated modification, defines its biosynthetic logic, and reveals a role for MNIO-modified proteins in bacterial oxidative stress defense.

PubMed: 42508400
DOI: 10.1016/j.chembiol.2026.06.014

Experimental method

X-RAY DIFFRACTION (2 Å)