 |
PDBsum entry 1jii
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of staphylococcus aureus tyrosyl-Trna synthetase in complex with a class of potent and specific inhibitors.
|
|
|
Authors
|
|
X.Qiu,
C.A.Janson,
W.W.Smith,
S.M.Green,
P.Mcdevitt,
K.Johanson,
P.Carter,
M.Hibbs,
C.Lewis,
A.Chalker,
A.Fosberry,
J.Lalonde,
J.Berge,
P.Brown,
C.S.Houge-Frydrych,
R.L.Jarvest.
|
|
|
Ref.
|
|
Protein Sci, 2001,
10,
2008-2016.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
SB-219383 and its analogues are a class of potent and specific inhibitors of
bacterial tyrosyl-tRNA synthetases. Crystal structures of these inhibitors have
been solved in complex with the tyrosyl-tRNA synthetase from Staphylococcus
aureus, the bacterium that is largely responsible for hospital-acquired
infections. The full-length enzyme yielded crystals that diffracted to 2.8 A
resolution, but a truncated version of the enzyme allowed the resolution to be
extended to 2.2 A. These inhibitors not only occupy the known substrate binding
sites in unique ways, but also reveal a butyl binding pocket. It was reported
that the Bacillus stearothermophilus TyrRS T51P mutant has much increased
catalytic activity. The S. aureus enzyme happens to have a proline at position
51. Therefore, our structures may contribute to the understanding of the
catalytic mechanism and provide the structural basis for designing novel
antimicrobial agents.
|
|
|
|
|
|
|
|
Figure 7.
Fig. 7. The binding of SB-284485 to YRS. (A) Schematic
diagram showing all the hydrogen bonding interactions (dashed
lines) between the inhibitor and YRS. The hydrogen bonding
distances are labeled. (B) Stereoview of the fucose binding
mode. Hydrogen bonds are shown in dashed lines. SB-243545 is
included for comparison. Protein carbons are in yellow,
SB-284485 carbons are in purple, and SB-243545 carbons are in
grey. Oxygen is red and nitrogen is cyan. (C) Stereoview of the
superposition of SB-284485 (purple) and tyrosyl adenylate
(green). The latter is shown with ribose hydrogen bonds and is
modeled based on bsTyrRS structures.
|
|
Figure 8.
Fig. 8. Stereoviews of the Electron Density (2Fo-Fc) Maps
for the YRS Inhibitors. (A) The density for SB-219383 contoured
at 1  . (B) The
density of SB239629 contoured at 1 . (C) The
density for SB-243545 contoured at 1 . (D) The
density for SB-284485 contoured at 1.5 .
|
|
|
|
|
|
The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2001,
10,
2008-2016)
copyright 2001.
|
|
|
|
|
|
|
