Interaction of tyrosyl aryl dipeptides with S. aureus tyrosyl tRNA synthetase: inhibition and crystal structure of a complex.
Tyrosyl aryl dipeptide inhibitors of S. aureus tyrosyl tRNA synthetase have been identified with IC50 values down to 0.5 microM. A crystal structure of the enzyme complexed to one of the inhibitors shows occupancy of the tyrosyl binding pocket coupled with inhibitor interactions to key catalytic residues.
Jarvest
R L
RL
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Richard_L_Jarvest@sbphrd.com
Berge
J M
JM
Houge-Frydrych
C S
CS
Janson
C
C
Mensah
L M
LM
O'Hanlon
P J
PJ
Pope
A
A
Saldanha
A
A
Qiu
X
X
D001665:Binding Sites; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000201:enzymology*; D014443:Tyrosine / Q000031:analogs & derivatives; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000737:chemistry*
D004151:Dipeptides; D004791:Enzyme Inhibitors; D014443:Tyrosine; D014448:Tyrosine-tRNA Ligase; D005998:Glycine