View source for 7jt6


==Mycobacterium tuberculosis dethiobiotin synthetase in complex with Tetrazole 2==
<StructureSection load='7jt6' size='340' side='right'caption='[[7jt6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jt6]] is a 4 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=7JT6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JT6 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]] 2&#8491;</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=VJG:{(1S,2R)-2-[4-(1H-tetrazol-5-yl)benzene-1-carbonyl]cyclopentyl}acetic+acid'>VJG</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=7jt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jt6 OCA], [https://pdbe.org/7jt6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jt6 RCSB], [https://www.ebi.ac.uk/pdbsum/7jt6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jt6 ProSAT]</span></td></tr>
</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> 
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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7jt6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dethiobiotin synthetase 3D structures|Dethiobiotin synthetase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Bean JH]]
[[Category: Bruning JB]]
[[Category: Pederick JP]]