Structural basis of Streptococcus pyogenes immunity to its NAD+ glycohydrolase toxin.

ABSTRACT: The virulence of Gram-positive bacteria is enhanced by toxins like the Streptococcus pyogenes β-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 β-NAD(+). The protective effect of IFS involves an extensive interaction with the SPN active site that blocks access to β-NAD(+). The conformation of IFS changes upon binding to SPN, with repacking of an extended C-te

SUBMITTER: Smith CL 

PROVIDER: S-EPMC3056158 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature