Structural and enzymatic characterization of a host-specificity determinant from Salmonella

A. C. Kohler, S. Spano, J. E. Galan, C. E. Stebbins

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

GtgE is an effector protein from Salmonella Typhimurium that modulates trafficking of the Salmonella-containing vacuole. It exerts its function by cleaving the Rab-family GTPases Rab29, Rab32 and Rab38, thereby preventing the delivery of antimicrobial factors to the bacteria containing vacuole. Here, the crystal structure of GtgE at 1.65 angstrom resolution is presented, and structure-based mutagenesis and in vivo infection assays are used to identify its catalytic triad. A panel of cysteine protease inhibitors were examined and it was determined that N-ethylmaleimide, antipain and chymostatin inhibit GtgE activity in vitro. These findings provide the basis for the development of novel therapeutic strategies to combat Salmonella infections.

Original languageEnglish
Pages (from-to)384-391
Number of pages8
JournalActa crystallographica. Section D, Biological crystallography
Volume70
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • NEDD8 deamidation
  • crystal-structure
  • ubiquitin
  • typhi
  • pathway
  • deubiquitinase
  • typhimurium
  • acetylation
  • inhibitors
  • refinement
  • cysteine proteases
  • GtgE
  • Rab GTPase
  • Salmonella typhi
  • Salmonella typhimurium

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