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Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):384-91. doi: 10.1107/S1399004713028393. Epub 2014 Jan 29.

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

Author information

1
Laboratory of Structural Microbiology, Rockefeller University, New York, NY 10065, USA.
2
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.

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 Å 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.

KEYWORDS:

GtgE; Rab GTPase; Salmonella Typhi; Salmonella Typhimurium; cysteine proteases

PMID:
24531472
PMCID:
PMC3940199
DOI:
10.1107/S1399004713028393
[Indexed for MEDLINE]
Free PMC Article

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