Structural analysis of the peptidoglycan DL-endopeptidase CwlO complexed with its inhibitory protein IseA.
hydrophobic pocket for IseA binding
inhibition of DL‐endopeptidase
peptidoglycan degradation
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
05 Jun 2024
05 Jun 2024
Historique:
revised:
08
03
2024
received:
04
09
2023
accepted:
28
05
2024
medline:
6
6
2024
pubmed:
6
6
2024
entrez:
6
6
2024
Statut:
aheadofprint
Résumé
Peptidoglycan DL-endopeptidases locally cleave the peptide stem of peptidoglycan in the bacterial cell wall. This process facilitates bacterial growth and division by loosening the rigid peptidoglycan layer. IseA binds to the active site of multiple DL-endopeptidases and inhibits excessive peptidoglycan degradation that leads to cell lysis. To better understand how IseA inhibits DL-endopeptidase activity, we determined the crystal structure of the peptidoglycan DL-endopeptidase CwlO/IseA complex and compared it with that of the peptidoglycan DL-endopeptidase LytE/IseA complex. Structural analyses showed significant differences between the hydrophobic pocket-binding residues of the DL-endopeptidases (F361 of CwlO and W237 of LytE). Additionally, binding assays showed that the F361 mutation of CwlO to the bulkier hydrophobic residue, tryptophan, increased its binding affinity for IseA, whereas mutation to alanine reduced the affinity. These analyses revealed that the hydrophobic pocket-binding residue of DL-endopeptidases determines IseA-binding affinity and is required for substrate-mimetic inhibition by IseA.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research Foundation of Korea
ID : 2022R1A5A1031361
Organisme : National Research Foundation of Korea
ID : RS-2023-00301974
Organisme : National Research Foundation of Korea
ID : RS-2024-00334946
Informations de copyright
© 2024 Federation of European Biochemical Societies.
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