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Figure 6
A model of the induced-fit mechanism in ligand binding. Our structural characterization suggests that MtMetRS employs a induced-fit mechanism in ligand binding. In the F-state structure (left) the methionine pocket (MP) does not form and the AMP pocket (Ad) is too narrow to accommodate adenosine. The CP domain is in an open conformation and the KMSKS loop is disordered. In the presence of methionine and ATP, the intermediate product Met-AMP is generated and it accommodates substrate pockets (right). Met-AMP induces the formation of MP and Ad pockets, the architectures of which restore a normal conformation similar to other P-state MtMetRS structures. The CP domain shifts to a closed conformation and the KMSKS loop becomes highly disordered. Owing to the large conformational rearrangements that occur in the F-state structure, F-state MtMetRS exhibits a nonproductive conformation and a new pocket forms on the opposite side to the active site, providing a possible strategy for inhibitor design. Details of the new pocket formed in the F-state structure are shown in Supplementary Fig. S5(e).

IUCrJ
Volume 5| Part 4| July 2018| Pages 478-490
ISSN: 2052-2525
https://doi.org/10.1107/S2052252518008217