5xds
From Proteopedia
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<StructureSection load='5xds' size='340' side='right'caption='[[5xds]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='5xds' size='340' side='right'caption='[[5xds]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5xds]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XDS OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5xds]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XDS FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=83O:(2S)-2-azanyl-3-(4H-1,2,4-triazol-3-yl)propanoic+acid'>83O</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=83O:(2S)-2-azanyl-3-(4H-1,2,4-triazol-3-yl)propanoic+acid'>83O</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hisB, Rv1601, MTCY336.03c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Imidazoleglycerol-phosphate_dehydratase Imidazoleglycerol-phosphate dehydratase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.19 4.2.1.19] </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=5xds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xds OCA], [https://pdbe.org/5xds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xds RCSB], [https://www.ebi.ac.uk/pdbsum/5xds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xds ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), employs ten enzymes including imidazoleglycerol-phosphate dehydratase (IGPD) for de novo biosynthesis of histidine. The absence of histidine-biosynthesis in humans combined with its essentiality for Mtb makes the enzymes of this pathway major anti-TB drug targets. We explored the inhibitory potential of a small molecule beta-(1,2,4-Triazole-3-yl)-DL-alanine (DLA) against Mtb IGPD. DLA exhibits an in vitro inhibitory efficacy in the lower micromolar range. Higher-resolution crystal structures of native and substrate-bound Mtb IGPD provided additional structural features of this important drug target. Crystal structure of IGPD-DLA complex at a resolution of 1.75 A, confirmed that DLA locks down the function of the enzyme by binding in the active site pocket of the IGPD mimicking the substrate-binding mode to a high degree. In our biochemical study, DLA showed an efficient inhibition of Mtb IGPD. Furthermore, DLA also showed bactericidal activity against Mtb and Mycobacterium smegmatis and inhibited their growth in respective culture medium. Importantly, owing to the favorable ADME and physicochemical properties, it serves as an important lead molecule for further derivatizations. | ||
| + | |||
| + | Characterization of a triazole scaffold compound as an inhibitor of Mycobacterium tuberculosis imidazoleglycerol-phosphate dehydratase.,Kumar D, Jha B, Bhatia I, Ashraf A, Dwivedy A, Biswal BK Proteins. 2021 Jul 20. doi: 10.1002/prot.26181. PMID:34288118<ref>PMID:34288118</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5xds" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Imidazoleglycerol-phosphate dehydratase]] | [[Category: Imidazoleglycerol-phosphate dehydratase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Myctu]] | ||
[[Category: Ahangar, M S]] | [[Category: Ahangar, M S]] | ||
[[Category: Jha, B]] | [[Category: Jha, B]] | ||
Revision as of 06:22, 25 August 2021
Crystal structure of Mycobacterium tuberculosis HisB bound with an inhibitor
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