7l1j
From Proteopedia
(Difference between revisions)
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==Mycobacterium tuberculosis dethiobiotin synthetase in complex with Tetrazole 1== | ==Mycobacterium tuberculosis dethiobiotin synthetase in complex with Tetrazole 1== | ||
| - | <StructureSection load='7l1j' size='340' side='right'caption='[[7l1j]]' scene=''> | + | <StructureSection load='7l1j' size='340' side='right'caption='[[7l1j]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L1J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7l1j]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L1J FirstGlance]. <br> |
| - | </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=7l1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l1j OCA], [https://pdbe.org/7l1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l1j RCSB], [https://www.ebi.ac.uk/pdbsum/7l1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l1j ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XES:{(1R,2R)-2-[4-(1H-tetrazol-5-yl)benzene-1-carbonyl]cyclopentyl}propanedioic+acid'>XES</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6nmz|6nmz]], [[6nwg|6nwg]], [[6nnz|6nnz]], [[6nu6|6nu6]], [[6nvc|6nvc]], [[6nve|6nve]], [[6nvf|6nvf]], [[7jt6|7jt6]], [[7jt5|7jt5]]</div></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dethiobiotin_synthase Dethiobiotin synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.3.3 6.3.3.3] </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=7l1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l1j OCA], [https://pdbe.org/7l1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l1j RCSB], [https://www.ebi.ac.uk/pdbsum/7l1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l1j ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/BIOD_MYCTU BIOD_MYCTU]] Catalyzes a mechanistically unusual reaction, the ATP-dependent insertion of CO2 between the N7 and N8 nitrogen atoms of 7,8-diaminopelargonic acid (DAPA) to form an ureido ring.<ref>PMID:20565114</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mycobacterium tuberculosis dethiobiotin synthase (MtDTBS) is a crucial enzyme involved in the biosynthesis of biotin in the causative agent of tuberculosis, M. tuberculosis. Here, we report a binder of MtDTBS, cyclopentylacetic acid 2 (KD = 3.4 +/- 0.4 mM), identified via in silico screening. X-ray crystallography showed that 2 binds in the 7,8-diaminopelargonic acid (DAPA) pocket of MtDTBS. Appending an acidic group to the para-position of the aromatic ring of the scaffold revealed compounds 4c and 4d as more potent binders, with KD = 19 +/- 5 and 17 +/- 1 muM, respectively. Further optimization identified tetrazole 7a as a particularly potent binder (KD = 57 +/- 5 nM) and inhibitor (Ki = 5 +/- 1 muM) of MtDTBS. Our findings highlight the first reported inhibitors of MtDTBS and serve as a platform for the further development of potent inhibitors and novel therapeutics for the treatment of tuberculosis. | ||
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| + | Inhibition of Mycobacterium tuberculosis Dethiobiotin Synthase (MtDTBS): Toward Next-Generation Antituberculosis Agents.,Schumann NC, Lee KJ, Thompson AP, Salaemae W, Pederick JL, Avery T, Gaiser BI, Hodgkinson-Bean J, Booker GW, Polyak SW, Bruning JB, Wegener KL, Abell AD ACS Chem Biol. 2021 Sep 17. doi: 10.1021/acschembio.1c00491. PMID:34533923<ref>PMID:34533923</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7l1j" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Dethiobiotin synthase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bruning | + | [[Category: Bruning, J B]] |
| - | [[Category: Pederick | + | [[Category: Pederick, J L]] |
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Ligase]] | ||
Revision as of 06:28, 1 December 2021
Mycobacterium tuberculosis dethiobiotin synthetase in complex with Tetrazole 1
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