7B3A

Crystal structure of PamZ

Summary for 7B3A

• Entry DOI: 10.2210/pdb7b3a/pdb
• Descriptor: Putative Acyl-transferase domain protein, ACETYL COENZYME *A, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: gcn5-related n-acetyltransferase-like protein; paenilamicin; paenilamicin-gene cluster, transferase
• Biological source: Paenibacillus larvae subsp. larvae
• Total number of polymer chains: 1
• Total formula weight: 33175.90

Authors

Loll, B.,Dang, T.,Mainz, A.,Suessmuth, R.,Wahl, M.C. (deposition date: 2020-11-30, release date: 2021-11-10, Last modification date: 2024-01-31)

Primary citation

Dang, T.,Loll, B.,Muller, S.,Skobalj, R.,Ebeling, J.,Bulatov, T.,Gensel, S.,Gobel, J.,Wahl, M.C.,Genersch, E.,Mainz, A.,Sussmuth, R.D.
Molecular basis of antibiotic self-resistance in a bee larvae pathogen.
Nat Commun, 13:2349-2349, 2022

PubMed Abstract: Paenibacillus larvae, the causative agent of the devastating honey-bee disease American Foulbrood, produces the cationic polyketide-peptide hybrid paenilamicin that displays antibacterial and antifungal activity. Its biosynthetic gene cluster contains a gene coding for the N-acetyltransferase PamZ. We show that PamZ acts as self-resistance factor in Paenibacillus larvae by deactivation of paenilamicin. Using tandem mass spectrometry, nuclear magnetic resonance spectroscopy and synthetic diastereomers, we identified the N-terminal amino group of the agmatinamic acid as the N-acetylation site. These findings highlight the pharmacophore region of paenilamicin, which we very recently identified as a ribosome inhibitor. Here, we further determined the crystal structure of PamZ:acetyl-CoA complex at 1.34 Å resolution. An unusual tandem-domain architecture provides a well-defined substrate-binding groove decorated with negatively-charged residues to specifically attract the cationic paenilamicin. Our results will help to understand the mode of action of paenilamicin and its role in pathogenicity of Paenibacillus larvae to fight American Foulbrood.

PubMed: 35487884
DOI: 10.1038/s41467-022-29829-w

Experimental method

X-RAY DIFFRACTION (1.34 Å)