9SN1

Lip3 DL-peptidase in the apo-state

Summary for 9SN1

• Entry DOI: 10.2210/pdb9sn1/pdb
• Descriptor: Beta-lactamase family protein (2 entities in total)
• Functional Keywords: dl-peptidase, paenibacillus, syringafactin, hydrolase
• Biological source: Paenibacillus
• Total number of polymer chains: 1
• Total formula weight: 72263.63

Authors

Schindelin, H. (deposition date: 2025-09-09, release date: 2026-02-18, Last modification date: 2026-02-25)

Primary citation

Zhang, S.,Huang, Y.,Schlabach, K.,Tran, M.A.,Nachawati, R.,Bader, N.,Komor, A.J.,Hertweck, C.,Schindelin, H.,Lakemeyer, M.,Hellmich, U.A.,Stallforth, P.
Microbial dl-Peptidases Enable Predator Defense and Facilitate Structure Elucidation of Complex Natural Products.
J.Am.Chem.Soc., 148:5264-5274, 2026

PubMed Abstract: Peptidases are indispensable tools in biotechnology and chemical biology. However, the enzyme repertoire for the selective hydrolysis of dl-amide bonds in peptides is small. Here, we describe novel dl-peptidases that mediate complex microbial interactions. These enzymes, Lip3 and Lip7, convert lipopeptides into potent amoebicidal agents via selective dl-peptide bond cleavage. Using structural analyses and mutagenesis, we identified an unusual Ser-Lys-Lys-Tyr catalytic tetrad required for dl-specificity. Despite their high structural similarity, both enzymes show distinct substrate preferences: Lip3 acts primarily as a carboxypeptidase, removing a single C-terminal residue, while Lip7 excises a tripeptide. Although their substrate scopes are broad, they are highly specific with regard to their respective cutting sites. These features make these dl-peptidases powerful tools for elucidating the structure of complex peptide-based natural products, including tensin and WLIP. Overall, this work elucidates the molecular mechanisms of cooperative microbial defense and provides a new enzymatic toolbox for biocatalysis and natural product discovery.

PubMed: 41615899
DOI: 10.1021/jacs.5c17955

Experimental method

X-RAY DIFFRACTION (2.04 Å)