5xet
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==Crystal structure of Mycobacterium tuberculosis methionyl-tRNA synthetase bound by methionyl-adenylate (Met-AMP)== | ==Crystal structure of Mycobacterium tuberculosis methionyl-tRNA synthetase bound by methionyl-adenylate (Met-AMP)== | ||
- | <StructureSection load='5xet' size='340' side='right' caption='[[5xet]], [[Resolution|resolution]] 2.38Å' scene=''> | + | <StructureSection load='5xet' size='340' side='right'caption='[[5xet]], [[Resolution|resolution]] 2.38Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[5xet]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XET OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5xet]] is a 1 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=5XET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XET FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ME8:[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL]+(2S)-2-AZANYL-4-METHYLSULFANYL-BUTANOATE'>ME8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38Å</td></tr> |
- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ME8:[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL]+(2S)-2-AZANYL-4-METHYLSULFANYL-BUTANOATE'>ME8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xet OCA], [https://pdbe.org/5xet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xet RCSB], [https://www.ebi.ac.uk/pdbsum/5xet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xet ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
- | [ | + | [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;"> | ||
+ | == 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<ref>PMID:30002848</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 5xet" style="background-color:#fffaf0;"></div> | ||
+ | |||
+ | ==See Also== | ||
+ | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
- | [[Category: | + | [[Category: Large Structures]] |
- | [[Category: Cui | + | [[Category: Mycobacterium tuberculosis H37Ra]] |
- | [[Category: Gao | + | [[Category: Cui S]] |
- | [[Category: Qin | + | [[Category: Gao X]] |
- | [[Category: Wang | + | [[Category: Qin B]] |
- | [[Category: Wang | + | [[Category: Wang M]] |
- | [[Category: Wojdyla | + | [[Category: Wang W]] |
- | + | [[Category: Wojdyla JA]] | |
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Current revision
Crystal structure of Mycobacterium tuberculosis methionyl-tRNA synthetase bound by methionyl-adenylate (Met-AMP)
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