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| | ==Crystal structure of apo form (free-state) Mycobacterium tuberculosis methionyl-tRNA synthetase== | | ==Crystal structure of apo form (free-state) Mycobacterium tuberculosis methionyl-tRNA synthetase== |
| - | <StructureSection load='5xgq' size='340' side='right' caption='[[5xgq]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5xgq' size='340' side='right'caption='[[5xgq]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xgq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycta Mycta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XGQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xgq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Ra Mycobacterium tuberculosis H37Ra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XGQ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">metG, MRA_1016 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=419947 MYCTA])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.899Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xgq OCA], [https://pdbe.org/5xgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xgq RCSB], [https://www.ebi.ac.uk/pdbsum/5xgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xgq ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xgq OCA], [http://pdbe.org/5xgq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xgq RCSB], [http://www.ebi.ac.uk/pdbsum/5xgq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xgq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A5U150_MYCTA A5U150_MYCTA]] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.[HAMAP-Rule:MF_01228] | + | [https://www.uniprot.org/uniprot/A5U150_MYCTA A5U150_MYCTA] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.[HAMAP-Rule:MF_01228] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5xgq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5xgq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Methionine--tRNA ligase]] | + | [[Category: Large Structures]] |
| - | [[Category: Mycta]] | + | [[Category: Mycobacterium tuberculosis H37Ra]] |
| - | [[Category: Cui, S]] | + | [[Category: Cui S]] |
| - | [[Category: Wang, M]] | + | [[Category: Wang M]] |
| - | [[Category: Wang, W]] | + | [[Category: Wang W]] |
| - | [[Category: Wojdyla, J A]] | + | [[Category: Wojdyla JA]] |
| - | [[Category: Anticodon-binding domain of trna]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Methionyl-trna synthetase]]
| + | |
| - | [[Category: Mycobacterium tuberculosis]]
| + | |
| - | [[Category: Protein translation]]
| + | |
| Structural highlights
Function
A5U150_MYCTA Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.[HAMAP-Rule:MF_01228]
Publication Abstract from PubMed
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 A resolution) and a structure with the intermediate product methionyl-adenylate (Met-AMP) bound (2.4 A 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.
Structural characterization of free-state and product-state Mycobacterium tuberculosis methionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism.,Wang W, Qin B, Wojdyla JA, Wang M, Gao X, Cui S IUCrJ. 2018 Jun 22;5(Pt 4):478-490. doi: 10.1107/S2052252518008217. eCollection, 2018 Jul 1. PMID:30002848[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang W, Qin B, Wojdyla JA, Wang M, Gao X, Cui S. Structural characterization of free-state and product-state Mycobacterium tuberculosis methionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism. IUCrJ. 2018 Jun 22;5(Pt 4):478-490. doi: 10.1107/S2052252518008217. eCollection, 2018 Jul 1. PMID:30002848 doi:http://dx.doi.org/10.1107/S2052252518008217
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