Flexibility and communication within the structure of the Mycobacterium smegmatis methionyl-tRNA synthetase.
Two structures of monomeric methionyl-tRNA synthetase, from Mycobacterium smegmatis, in complex with the ligands methionine/adenosine and methionine, were analyzed by X-ray crystallography at 2.3 Å and at 2.8 Å, respectively. The structures demonstrated the flexibility of the multidomain enzyme. A new conformation of the structure was identified in which the connective peptide domain bound more closely to the catalytic domain than described previously. The KMSKS(301-305) loop in our structures was in an open and inactive conformation that differed from previous structures by a rotation of the loop of about 90° around hinges located at Asn297 and Val310. The binding of adenosine to the methionyl-tRNA synthetase methionine complex caused a shift in the KMSKS domain that brought it closer to the catalytic domain. The potential use of the adenosine-binding site for inhibitor binding was evaluated and a potential binding site for a specific allosteric inhibitor was identified.
Ingvarsson
Henrik
H
Department of Cell and Molecular Biology, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
Unge
Torsten
T
D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D016018:Least-Squares Analysis; D008715:Methionine / Q000378:metabolism; D008718:Methionine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D020102:Mycobacterium smegmatis / Q000201:enzymology*; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D011487:Protein Conformation; D016963:Thermus thermophilus / Q000201:enzymology
D000255:Adenosine Triphosphate; D008715:Methionine; D008718:Methionine-tRNA Ligase; D000241:Adenosine