5XET

Crystal structure of Mycobacterium tuberculosis methionyl-tRNA synthetase bound by methionyl-adenylate (Met-AMP)

Summary for 5XET

• Entry DOI: 10.2210/pdb5xet/pdb
• Descriptor: Methionine--tRNA ligase, [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] (2S)-2-azanyl-4-methylsulfanyl-butanoate, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: synthetase, aminoacyl-trna synthetase, complex, atp, ligase
• Biological source: Mycobacterium tuberculosis H37Ra
• Total number of polymer chains: 1
• Total formula weight: 60081.83

Authors

Wang, W.,Qin, B.,Wojdyla, J.A.,Wang, M.,Gao, X.,Cui, S. (deposition date: 2017-04-06, 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

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: 30002848
DOI: 10.1107/S2052252518008217

Experimental method

X-RAY DIFFRACTION (2.38 Å)