7LKC

Crystal Structure of Keratinimicin A

7LKC の概要

• エントリーDOI: 10.2210/pdb7lkc/pdb
• 分子名称: Keratinimicin A peptide moiety, alpha-L-rhamnopyranose-(1-2)-beta-D-glucopyranose, alpha-D-mannopyranose, ... (7 entities in total)
• 機能のキーワード: glycopeptide, antibiotic, actinomycete, biosynthesis
• 由来する生物種: Amycolatopsis keratiniphila
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 3872.83

構造登録者

Davis, K.M.,Jeffrey, P.D.,Seyedsayamdost, M.R. (登録日: 2021-02-02, 公開日: 2022-12-07, 最終更新日: 2024-07-24)

主引用文献

Chioti, V.T.,McWhorter, K.L.,Blue, T.C.,Li, Y.,Xu, F.,Jeffrey, P.D.,Davis, K.M.,Seyedsayamdost, M.R.
Potent and specific antibiotic combination therapy against Clostridioides difficile.
Nat.Chem.Biol., 20:924-933, 2024

PubMed Abstract: Keratinicyclins and keratinimicins are recently discovered glycopeptide antibiotics. Keratinimicins show broad-spectrum activity against Gram-positive bacteria, while keratinicyclins form a new chemotype by virtue of an unusual oxazolidinone moiety and exhibit specific antibiosis against Clostridioides difficile. Here we report the mechanism of action of keratinicyclin B (KCB). We find that steric constraints preclude KCB from binding peptidoglycan termini. Instead, KCB inhibits C. difficile growth by binding wall teichoic acids (WTAs) and interfering with cell wall remodeling. A computational model, guided by biochemical studies, provides an image of the interaction of KCB with C. difficile WTAs and shows that the same H-bonding framework used by glycopeptide antibiotics to bind peptidoglycan termini is used by KCB for interacting with WTAs. Analysis of KCB in combination with vancomycin (VAN) shows highly synergistic and specific antimicrobial activity, and that nanomolar combinations of the two drugs are sufficient for complete growth inhibition of C. difficile, while leaving common commensal strains unaffected.

PubMed: 38942968
DOI: 10.1038/s41589-024-01651-z

実験手法

X-RAY DIFFRACTION (0.95 Å)