5XGQ
Crystal structure of apo form (free-state) Mycobacterium tuberculosis methionyl-tRNA synthetase
Summary for 5XGQ
| Entry DOI | 10.2210/pdb5xgq/pdb |
| Descriptor | Methionine-tRNA ligase (2 entities in total) |
| Functional Keywords | methionyl-trna synthetase, protein translation, mycobacterium tuberculosis, anticodon-binding domain of trna, ligase |
| Biological source | Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra) |
| Total number of polymer chains | 2 |
| Total formula weight | 120497.42 |
| Authors | Wang, W.,Wang, M.,Wojdyla, J.A.,Cui, S. (deposition date: 2017-04-15, release date: 2018-07-11, Last modification date: 2023-11-22) |
| Primary citation | Wang, W.,Qin, B.,Wojdyla, J.A.,Wang, M.,Gao, X.,Cui, S. Structural characterization of free-state and product-stateMycobacterium tuberculosismethionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism IUCrJ, 5:478-490, 2018 Cited by PubMed Abstract: (MTB) caused 10.4 million cases of tuberculosis and 1.7 million deaths in 2016. The incidence of multidrug-resistant and extensively drug-resistant MTB is becoming an increasing threat to public health and the development of novel anti-MTB drugs is urgently needed. Methionyl-tRNA synthetase (MetRS) is considered to be a valuable drug target. However, structural characterization of MetRS (MtMetRS) was lacking for decades, thus hampering drug design. Here, two high-resolution crystal structures of MtMetRS are reported: the free-state structure (apo form; 1.9 Å resolution) and a structure with the intermediate product methionyl-adenylate (Met-AMP) bound (2.4 Å resolution). It was found that free-state MtMetRS adopts a previously unseen conformation that has never been observed in other MetRS homologues. The pockets for methionine and AMP are not formed in free-state MtMetRS, suggesting that it is in a nonproductive conformation. Combining these findings suggests that MtMetRS employs an induced-fit mechanism in ligand binding. By comparison with the structure of human cytosolic MetRS, additional pockets specific to MtMetRS that could be used for anti-MTB drug design were located. PubMed: 30002848DOI: 10.1107/S2052252518008217 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.899 Å) |
Structure validation
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