7jt5: Difference between revisions
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<StructureSection load='7jt5' size='340' side='right'caption='[[7jt5]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='7jt5' size='340' side='right'caption='[[7jt5]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7jt5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7jt5]] 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=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='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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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='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> | <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 == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 7jt5" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7jt5" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Dethiobiotin synthetase 3D structures|Dethiobiotin synthetase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Bruning | [[Category: Bruning JB]] | ||
[[Category: Pederick | [[Category: Pederick JP]] | ||
Latest revision as of 18:10, 18 October 2023
Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9Mycobacterium tuberculosis dethiobiotin synthetase in complex with fragment analogue 9
Structural highlights
FunctionBIOD_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.[1] Publication Abstract from PubMedMycobacterium 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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