5XGQ

Crystal structure of apo form (free-state) Mycobacterium tuberculosis methionyl-tRNA synthetase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural characterization of free-state and product-stateMycobacterium tuberculosismethionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism

Wang, W.Qin, B.Wojdyla, J.A.Wang, M.Gao, X.Cui, S.

(2018) IUCrJ 5: 478-490

  • DOI: 10.1107/S2052252518008217
  • Primary Citation of Related Structures:  
    5XET, 5XGQ

  • PubMed Abstract: 
  • Mycobacterium tuberculosis (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 ...

    Mycobacterium tuberculosis (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 M. tuberculosis 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.


    Organizational Affiliation

    MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Science, No. 9 Dong Dan San Tiao, Dong Cheng Qu, Beijing 100730, People's Republic of China.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Methionine-tRNA ligaseB [auth A], A [auth B]535Mycobacterium tuberculosis H37RaMutation(s): 0 
Gene Names: metGMRA_1016
EC: 6.1.1.10
UniProt
Find proteins for A5U150 (Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra))
Explore A5U150 
Go to UniProtKB:  A5U150
Protein Feature View
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.983α = 98.9
b = 72.727β = 90.05
c = 78.376γ = 98.47
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-07-11
    Type: Initial release
  • Version 1.1: 2018-08-01
    Changes: Data collection, Database references