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 language | English |
|---|---|
| Pages (from-to) | 384-391 |
| Number of pages | 8 |
| Journal | Acta crystallographica. Section D, Biological crystallography |
| Volume | 70 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2014 |
Keywords
- NEDD8 deamidation
- crystal-structure
- ubiquitin
- typhi
- pathway
- deubiquitinase
- typhimurium
- acetylation
- inhibitors
- refinement
- cysteine proteases
- GtgE
- Rab GTPase
- Salmonella typhi
- Salmonella typhimurium
Cite this
Structural and enzymatic characterization of a host-specificity determinant from Salmonella. / Kohler, A. C.; Spano, S.; Galan, J. E.; Stebbins, C. E.
In: Acta crystallographica. Section D, Biological crystallography, Vol. 70, No. 2, 02.2014, p. 384-391.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural and enzymatic characterization of a host-specificity determinant from Salmonella
AU - Kohler, A. C.
AU - Spano, S.
AU - Galan, J. E.
AU - Stebbins, C. E.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - NEDD8 deamidation
KW - crystal-structure
KW - ubiquitin
KW - typhi
KW - pathway
KW - deubiquitinase
KW - typhimurium
KW - acetylation
KW - inhibitors
KW - refinement
KW - cysteine proteases
KW - GtgE
KW - Rab GTPase
KW - Salmonella typhi
KW - Salmonella typhimurium
U2 - 10.1107/S1399004713028393
DO - 10.1107/S1399004713028393
M3 - Article
VL - 70
SP - 384
EP - 391
JO - Acta crystallographica. Section D, Biological crystallography
JF - Acta crystallographica. Section D, Biological crystallography
SN - 0907-4449
IS - 2
ER -