NMR Shows Why a Small Chemical Change Almost Abolishes the Antimicrobial Activity of Glycocin F.
Biochemistry
; 62(17): 2669-2676, 2023 09 05.
Article
em En
| MEDLINE
| ID: mdl-37531216
ABSTRACT
Glycocin F (GccF), a ribosomally synthesized, post-translationally modified peptide secreted by Lactobacillus plantarum KW30, rapidly inhibits the growth of susceptible bacteria at nanomolar concentrations. Previous studies have highlighted structural features important for its activity and have shown the absolute requirement for the Ser18 O-linked GlcNAc on the eight-residue loop linking the two short helices of the (C-X6-C)2 structure. Here, we show that an ostensibly very small chemical modification to Ser18, the substitution of the Cα proton with a methyl group, reduces the antimicrobial activity of GccF 1000-fold (IC50 1.5 µM cf. 1.5 nM). A comparison of the GccFα-methylSer18 NMR structure (PDB 8DFZ) with that of the native protein (PDB 2KUY) showed a marked difference in the orientation and mobility of the loop, as well as a markedly different positioning of the GlcNAc, suggesting that loop conformation, dynamics, and glycan presentation play an important role in the interaction of GccF with as yet unknown but essential physiological target molecules.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Anti-Infecciosos
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Nova Zelândia