title: Interaction of tyrosyl aryl dipeptides with S. aureus tyrosyl tRNA synthetase: inhibition and crystal structure of a complex.
abstract: 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.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Richard_L_Jarvest@sbphrd.com
authors.forename: R L
authors.initials: RL
authors.lastname: Jarvest
authors.forename: J M
authors.initials: JM
authors.lastname: Berge
authors.forename: C S
authors.initials: CS
authors.lastname: Houge-Frydrych
authors.forename: C
authors.initials: C
authors.lastname: Janson
authors.forename: L M
authors.initials: LM
authors.lastname: Mensah
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Hanlon
authors.forename: A
authors.initials: A
authors.lastname: Pope
authors.forename: A
authors.initials: A
authors.lastname: Saldanha
authors.forename: X
authors.initials: X
authors.lastname: Qiu
mesh_terms: 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*
chemical_list: D004151:Dipeptides; D004791:Enzyme Inhibitors; D014443:Tyrosine; D014448:Tyrosine-tRNA Ligase; D005998:Glycine