In Vivo Probe of Lipidâ
II-Interacting Proteins.
Angew Chem Int Ed Engl
; 55(29): 8401-4, 2016 07 11.
Article
em En
| MEDLINE
| ID: mdl-27225706
ABSTRACT
ß-Lactams represent one of the most important classes of antibiotics discovered to date. These agents block Lipidâ
II processing and cell wall biosynthesis through inactivation of penicillin-binding proteins (PBPs). PBPs enzymatically load cell wall building blocks from Lipidâ
II carrier molecules onto the growing cell wall scaffold during growth and division. Lipidâ
II, a bottleneck in cell wall biosynthesis, is the target of some of the most potent antibiotics in clinical use. Despite the immense therapeutic value of this biosynthetic pathway, the PBP-Lipidâ
II association has not been established in live cells. To determine this key interaction, we designed an unnatural d-amino acid dipeptide that is metabolically incorporated into Lipidâ
II molecules. By hijacking the peptidoglycan biosynthetic machinery, photoaffinity probes were installed in combination with click partners within Lipidâ
II, thereby allowing, for the first time, demonstration of PBP interactions inâ
vivo with Lipidâ
II.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uridina Difosfato Ácido N-Acetilmurâmico
/
Proteínas de Ligação às Penicilinas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article