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<StructureSection load='6ax8' size='340' side='right'caption='[[6ax8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='6ax8' size='340' side='right'caption='[[6ax8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ax8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AX8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AX8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ax8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AX8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AX8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></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]] 2.6&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">metG, metS, Rv1007c, MTCI237.24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></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=6ax8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ax8 OCA], [https://pdbe.org/6ax8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ax8 RCSB], [https://www.ebi.ac.uk/pdbsum/6ax8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ax8 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=6ax8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ax8 OCA], [http://pdbe.org/6ax8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ax8 RCSB], [http://www.ebi.ac.uk/pdbsum/6ax8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ax8 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SYM_MYCTU SYM_MYCTU]] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.  
[https://www.uniprot.org/uniprot/SYM_MYCTU SYM_MYCTU] Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mycobacterium tuberculosis is a pathogenic bacterial infectious agent that is responsible for approximately 1.5 million human deaths annually. Current treatment requires the long-term administration of multiple medicines with substantial side effects. Lack of compliance, together with other factors, has resulted in a worrisome increase in resistance. New treatment options are therefore urgently needed. Here, the crystal structure of methionyl-tRNA synthetase (MetRS), an enzyme critical for protein biosynthesis and therefore a drug target, in complex with its catalytic intermediate methionyl adenylate is reported. Phenylalanine 292 of the M. tuberculosis enzyme is in an `out' conformation and barely contacts the adenine ring, in contrast to other MetRS structures where ring stacking occurs between the adenine and a protein side-chain ring in the `in' conformation. A comparison with human cytosolic MetRS reveals substantial differences in the active site as well as regarding the position of the connective peptide subdomain 1 (CP1) near the active site, which bodes well for arriving at selective inhibitors. Comparison with the human mitochondrial enzyme at the amino-acid sequence level suggests that arriving at inhibitors with higher affinity for the mycobacterial enzyme than for the mitochondrial enzyme might be achievable.
 
The crystal structure of the drug target Mycobacterium tuberculosis methionyl-tRNA synthetase in complex with a catalytic intermediate.,Barros-Alvarez X, Turley S, Ranade RM, Gillespie JR, Duster NA, Verlinde CLMJ, Fan E, Buckner FS, Hol WGJ Acta Crystallogr F Struct Biol Commun. 2018 Apr 1;74(Pt 4):245-254. doi:, 10.1107/S2053230X18003151. Epub 2018 Mar 28. PMID:29633973<ref>PMID:29633973</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ax8" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Methionine--tRNA ligase]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Myctu]]
[[Category: Barros-Alvarez X]]
[[Category: Barros-Alvarez, X]]
[[Category: Hol WGJ]]
[[Category: Hol, W G.J]]
[[Category: Ligase]]
[[Category: Ligase-aminoacyl adenylate complex]]
[[Category: Synthetase]]
Retrieved from "https://proteopedia.org/6ax8"