Cooperative structural dynamics and a novel fidelity mechanism in histidyl-tRNA synthetases.
The crystal structure of the Staphylococcus aureus histidyl-tRNA synthetase apoprotein has been determined at 2.7 A resolution. Several important loops in the active site either become disordered or adopt very different conformations compared to their ligand-bound states. These include the histidine A motif (Arg257-Tyr262) that is essential for substrate recognition, a loop (Gly52-Lys62) that seems to control the communication between the histidine and ATP binding sites, the motif 2 loop (Glu114-Arg120) that binds ATP, and the insertion domain that is likely to bind tRNA. These ligand-induced structural changes are supported by fluorescence experiments, which also suggest highly cooperative dynamics. A dynamic and cooperative active site is most likely necessary for the proper functioning of the histidyl-tRNA synthetase, and suggests a novel mechanism for improving charging fidelity.
Qiu
X
X
Department of Structural Biology, Department of Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. xiayang_qiu-1@sbphrd.com
Janson
C A
CA
Blackburn
M N
MN
Chhohan
I K
IK
Hibbs
M
M
Abdel-Meguid
S S
SS
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006643:Histidine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000201:enzymology; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D008024:Ligands; D006639:Histidine; D014364:Tryptophan; D006643:Histidine-tRNA Ligase