Structural and enzymatic characterization of a host-specificity determinant from Salmonella
- Rockefeller University, New York, NY 10065 (United States)
- Yale University School of Medicine, New Haven, CT 06536 (United States)
The Salmonella effector protein GtgE functions as a cysteine protease to cleave a subset of the Rab-family GTPases and to prevent delivery of antimicrobial agents to the Salmonella-containing vacuole. 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.
- OSTI ID:
- 22351307
- Journal Information:
- Acta Crystallographica. Section D: Biological Crystallography, Vol. 70, Issue Pt 2; Other Information: PMCID: PMC3940199; PMID: 24531472; PUBLISHER-ID: dw5076; OAI: oai:pubmedcentral.nih.gov:3940199; Copyright (c) International Union of Crystallography 2014; Country of input: International Atomic Energy Agency (IAEA); ISSN 0907-4449
- Country of Publication:
- Denmark
- Language:
- English
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