View source for 7sew


==M. tb EgtD in complex with HD6==
<StructureSection load='7sew' size='340' side='right'caption='[[7sew]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sew]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SEW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I:N-(cyclopent-3-ene-1-carbonyl)-L-histidine'>A1I</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PDO:1,3-PROPANDIOL'>PDO</scene></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=7sew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sew OCA], [https://pdbe.org/7sew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sew RCSB], [https://www.ebi.ac.uk/pdbsum/7sew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sew ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EGTD_MYCTU EGTD_MYCTU] Catalyzes the SAM-dependent triple methylation of the alpha-amino group of histidine to form hercynine, a step in the biosynthesis pathway of ergothioneine.[UniProtKB:A0R5M8]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ergothioneine (EGT) is a low molecular weight histidine betaine essential in all domains of life but only synthesized by selected few organisms. Synthesis of EGT by Mycobacterium tuberculosis (M. tb) is critical for maintaining bioenergetic homeostasis and protecting the bacterium from alkylating agents, oxidative stress, and anti-tubercular drugs. EgtD, an S-adenosylmethionine-dependent methyltransferase (AdoMet), catalyzes the trimethylation of L-Histidine to initiate EGT biosynthesis and this reaction has been shown to be essential for EGT production in mycobacteria and for long-term infection of murine macrophages by M. tb. In this work, library screening and structure-guided strategies identified multiple classes of M. tb EgtD inhibitors that bind in various regions of the enzyme active site. X-ray crystal structures of EgtD-inhibitor complexes confirm that L-Histidine analogs bind solely to the L-Histidine binding site while drug-like inhibitors, such as TGX-221, and S-Glycyl-H-1152 span both the L-Histidine and AdoMet binding sites. These enzyme-inhibitor complexes provide detailed structural information of compound scaffolds useful for developing more potent inhibitors that could shorten Tuberculosis treatment regimens by weakening important bacterial defenses.

Inhibitors of Mycobacterium tuberculosis EgtD target both substrate binding sites to limit hercynine production.,Sudasinghe TD, Banco MT, Ronning DR Sci Rep. 2021 Nov 15;11(1):22240. doi: 10.1038/s41598-021-01526-6. PMID:34782676<ref>PMID:34782676</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7sew" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Ronning DR]]
[[Category: Sudasinghe TD]]