Structural basis of Streptococcus pyogenes immunity to its NAD+ glycohydrolase toxin.
Structure
; 19(2): 192-202, 2011 Feb 09.
Article
en En
| MEDLINE
| ID: mdl-21300288
ABSTRACT
The virulence of Gram-positive bacteria is enhanced by toxins like the Streptococcus pyogenes ß-NAD(+) glycohydrolase known as SPN. SPN-producing strains of S. pyogenes additionally express the protein immunity factor for SPN (IFS), which forms an inhibitory complex with SPN. We have determined crystal structures of the SPN-IFS complex and IFS alone, revealing that SPN is structurally related to ADP-ribosyl transferases but lacks the canonical binding site for protein substrates. SPN is instead a highly efficient glycohydrolase with the potential to deplete cellular levels of ß-NAD(+). The protective effect of IFS involves an extensive interaction with the SPN active site that blocks access to ß-NAD(+). The conformation of IFS changes upon binding to SPN, with repacking of an extended C-terminal α helix into a compact shape. IFS is an attractive target for the development of novel bacteriocidal compounds functioning by blocking the bacterium's self-immunity to the SPN toxin.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Bacterianas
/
Toxinas Bacterianas
/
NAD/ Nucleosidasa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos