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Crystal structure of Staphylococcus aureus tyrosyl‐tRNA synthetase in complex with a class of potent and specific inhibitors
Author(s) -
Qiu Xiayang,
Janson Cheryl A.,
Smith Ward W.,
Green Susan M.,
McDevitt Patrick,
Johanson Kyung,
Carter Paul,
Hibbs Martin,
Lewis Ceri,
Chalker Alison,
Fosberry Andrew,
Lalonde Judith,
Berge John,
Brown Pamela,
HougeFrydrych Catherine S.V.,
Jarvest Richard L.
Publication year - 2001
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.18001
Subject(s) - enzyme , staphylococcus aureus , lyase , binding site , stereochemistry , biochemistry , hydrolase , bacteria , chemistry , biology , genetics
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 Å resolution, but a truncated version of the enzyme allowed the resolution to be extended to 2.2 Å. 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.