9b2e
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==DHNA associated with an inhibitor== | |
| + | <StructureSection load='9b2e' size='340' side='right'caption='[[9b2e]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9b2e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9B2E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B2E 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]] 1.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B55:2-AMINO-8-SULFANYL-1,9-DIHYDRO-6H-PURIN-6-ONE'>B55</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=9b2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b2e OCA], [https://pdbe.org/9b2e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b2e RCSB], [https://www.ebi.ac.uk/pdbsum/9b2e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b2e ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A045KE67_MYCTX A0A045KE67_MYCTX] Catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin.[RuleBase:RU362079] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The crystallographic structure of the FolB enzyme from Mycobacterium tuberculosis (MtFolB), complexed with its inhibitor 8-mercaptoguanine (8-MG), was elucidated at a resolution of 1.95 A. A novel series of S8-functionalized 8-MG derivatives were synthesised and evaluated as in vitro inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of MtFolB. These compounds exhibited IC(50) values in the submicromolar range. Evaluation of the activity for five compounds indicated their inhibition mode and inhibition constants. Molecular docking analyses were performed to determine the enzyme-inhibitor intermolecular interactions and ligand conformations upon complex formation. The inhibitory activities of all compounds against the M. tuberculosis H37Rv strain were evaluated. Compound 3e exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound 3e showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting MtFolB, an attractive molecular target for TB drug development. | ||
| - | + | Crystal structure of dihydroneopterin aldolase from Mycobacterium tuberculosis associated with 8-mercaptoguanine, and development of novel S8-functionalized analogues as inhibitors: Synthesis, enzyme inhibition, in vitro toxicity and antitubercular activity.,Czeczot AM, Muniz MN, Perello MA, Silva EED, Timmers LFSM, Berger A, Gonzalez LC, Arrache Goncalves G, Moura S, Machado P, Bizarro CV, Basso LA J Enzyme Inhib Med Chem. 2024 Dec;39(1):2388207. doi: , 10.1080/14756366.2024.2388207. Epub 2024 Aug 14. PMID:39140692<ref>PMID:39140692</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9b2e" style="background-color:#fffaf0;"></div> |
| - | [[Category: Basso | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Large Structures]] |
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Basso LA]] | ||
| + | [[Category: Bizarro CV]] | ||
| + | [[Category: Czeczot AM]] | ||
| + | [[Category: Machado P]] | ||
| + | [[Category: Silva EED]] | ||
| + | [[Category: Timmers LFSM]] | ||
Current revision
DHNA associated with an inhibitor
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