7jt5
From Proteopedia
(Difference between revisions)
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==Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9== | ==Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9== | ||
| - | <StructureSection load='7jt5' size='340' side='right'caption='[[7jt5]]' scene=''> | + | <StructureSection load='7jt5' size='340' side='right'caption='[[7jt5]], [[Resolution|resolution]] 2.00Å' 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=7JT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JT5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7jt5]] is a 4 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=7JT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JT5 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=7jt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jt5 OCA], [https://pdbe.org/7jt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jt5 RCSB], [https://www.ebi.ac.uk/pdbsum/7jt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jt5 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=VJS:{(1R,2R)-2-[4-(carboxymethyl)benzene-1-carbonyl]cyclopentyl}propanedioic+acid'>VJS</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;'>[[6nlz|6nlz]], [[6nmz|6nmz]], [[6nwg|6nwg]], [[6nnz|6nnz]], [[6nu6|6nu6]], [[6nvc|6nvc]], [[6nve|6nve]], [[6nvf|6nvf]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bioD, Rv1570, MTCY336.33c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=7jt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jt5 OCA], [https://pdbe.org/7jt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jt5 RCSB], [https://www.ebi.ac.uk/pdbsum/7jt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jt5 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 7jt5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Dethiobiotin synthase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bruning | + | [[Category: Myctu]] |
| - | [[Category: Pederick | + | [[Category: Bruning, J B]] |
| + | [[Category: Pederick, J P]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Ligase]] | ||
| + | [[Category: Ligase-ligase inhibitor complex]] | ||
Revision as of 09:00, 29 September 2021
Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9
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