9QFR

Crystal structure of Def1 in complex with actinonin

Summary for 9QFR

• Entry DOI: 10.2210/pdb9qfr/pdb
• Descriptor: Peptide deformylase 1, NICKEL (II) ION, ACTINONIN, ... (4 entities in total)
• Functional Keywords: metalloprotease, antibiotic, protein translation, hydrolase
• Biological source: Vibrio cholerae O1 biovar El Tor str. N16961
• Total number of polymer chains: 2
• Total formula weight: 41754.96

Authors

Mechaly, A.,Lamberioux, M.,Haouz, A.,Mazel, D. (deposition date: 2025-03-12, release date: 2025-12-10, Last modification date: 2025-12-24)

Primary citation

Lamberioux, M.,Ducos-Galand, M.,Kaminski, P.A.,Littner, E.,Betton, J.M.,Mechaly, A.,Haouz, A.,Mazel, D.
Unraveling the Prevalence and Multifaceted Roles of Accessory Peptide Deformylases in Bacterial Adaptation and Resistance.
Mol.Biol.Evol., 42:-, 2025

PubMed Abstract: Peptide deformylases (PDFs) are enzymes that are essential for bacterial viability and attractive targets for antibiotic development. Yet, despite their conserved function, many bacteria encode multiple PDFs, a genomic feature whose prevalence and implications remain largely unexplored. Here, we reveal that nearly half of all bacterial genomes carry more than one PDF gene, frequently embedded within mobile genetic elements such as plasmids and integrons. In Vibrio cholerae, the accessory PDF (Def2VCH) confers reduced susceptibility to actinonin (ACT), the most studied PDF inhibitor, while still supporting bacterial growth in the absence of the canonical PDF copies (Def1VCH). Crystallographic analysis shows that this reduced susceptibility stems from an arginine-to-tyrosine substitution that probably reduces ACT binding. Strikingly, this resistance signature is shared by integron-encoded PDFs, and transfer of an integron-encoded PDF cassette from Pseudoxanthomonas into a susceptible V. cholerae is sufficient to abolish ACT susceptibility. These findings reveal a hidden reservoir of resistance within the bacterial mobilome and shed light on potential mechanisms of bacterial resilience to environmental PDF inhibitors.

PubMed: 41316864
DOI: 10.1093/molbev/msaf311

Experimental method

X-RAY DIFFRACTION (1.52 Å)