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Structure of Pseudomonas aeruginosa aminopeptidase, PaAP
Structural highlights
FunctionLAP_PSEAE A secreted aminopeptidase. Acts on free N-terminal amino groups with a very strong preference for Leu- followed by Met- and Ala-, and no activity on Glu- or Gly- peptides (an exhaustive analysis was not performed). Both the AP56 and AP28 forms have activity.[1] Publication Abstract from PubMedPseudomonas aeruginosa is an opportunistic pathogen that causes serious illness, especially in immunocompromised individuals. P. aeruginosa forms biofilms that contribute to growth and persistence in a wide range of environments. Here we investigated the aminopeptidase, P. aeruginosa aminopeptidase (PaAP) from P. aeruginosa, which is highly abundant in the biofilm matrix. PaAP is associated with biofilm development and contributes to nutrient recycling. We confirmed that post-translational processing was required for activation and PaAP is a promiscuous aminopeptidase acting on unstructured regions of peptides and proteins. Crystal structures of wild-type enzymes and variants revealed the mechanism of autoinhibition, whereby the C-terminal propeptide locks the protease-associated domain and the catalytic peptidase domain into a self-inhibited conformation. Inspired by this, we designed a highly potent small cyclic-peptide inhibitor that recapitulates the deleterious phenotype observed with a PaAP deletion variant in biofilm assays and present a path toward targeting secreted proteins in a biofilm context. An anti-biofilm cyclic peptide targets a secreted aminopeptidase from P. aeruginosa.,Harding CJ, Bischoff M, Bergkessel M, Czekster CM Nat Chem Biol. 2023 Sep;19(9):1158-1166. doi: 10.1038/s41589-023-01373-8. Epub , 2023 Jun 29. PMID:37386135[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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