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)==
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<StructureSection load='5xet' size='340' side='right' caption='[[5xet]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
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<StructureSection load='5xet' size='340' side='right'caption='[[5xet]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XET FirstGlance]. <br>
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<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>
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</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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
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<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>
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<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>
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<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=5xet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xet OCA], [http://pdbe.org/5xet PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xet RCSB], [http://www.ebi.ac.uk/pdbsum/5xet PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xet ProSAT]</span></td></tr>
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<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 ==
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[[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]
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[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]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5xet" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Methionine--tRNA ligase]]
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[[Category: Large Structures]]
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[[Category: Cui, S]]
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[[Category: Mycobacterium tuberculosis H37Ra]]
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[[Category: Gao, X]]
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[[Category: Cui S]]
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[[Category: Qin, B]]
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[[Category: Gao X]]
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[[Category: Wang, M]]
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[[Category: Qin B]]
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[[Category: Wang, W]]
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[[Category: Wang M]]
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[[Category: Wojdyla, J A]]
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[[Category: Wang W]]
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[[Category: Aminoacyl-trna synthetase]]
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[[Category: Wojdyla JA]]
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[[Category: Atp]]
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[[Category: Complex]]
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[[Category: Ligase]]
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[[Category: Synthetase]]
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Current revision

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

PDB ID 5xet

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