Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S

Douglas A. Mitchell, Shaun W. Lee, Morgan A. Pence, Andrew L. Markley, Joyce D. Limm, Victor Nizet, Jack E. Dixon

Research output: Contribution to journalArticlepeer-review

Abstract

The human pathogen Streptococcus pyogenes secretes a highly cytolytic toxin known as streptolysin S (SLS). SLS is a key virulence determinant and responsible for the β-hemolytic phenotype of these bacteria. Despite over a century of research, the chemical structure of SLS remains unknown. Recent experiments have revealed that SLS is generated from an inactive precursor peptide that undergoes extensive post-translational modification to an active form. In this work, we address outstanding questions regarding the SLS biosynthetic process, elucidating the features of substrate recognition and sites of posttranslational modification to the SLS precursor peptide. Further, we exploit these findings to guide the design of artificial cytolytic toxins that are recognized by the SLS biosynthetic enzymes and others that are intrinsically cytolytic. This new structural information has ramifications for future antimicrobial therapies.

Original languageEnglish (US)
Pages (from-to)13004-13012
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number19
DOIs
StatePublished - May 8 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S'. Together they form a unique fingerprint.

Cite this