7ca1
From Proteopedia
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==Crystal structure of dihydroorotase in complex with plumbagin from Saccharomyces cerevisiae== | ==Crystal structure of dihydroorotase in complex with plumbagin from Saccharomyces cerevisiae== | ||
| - | <StructureSection load='7ca1' size='340' side='right'caption='[[7ca1]]' scene=''> | + | <StructureSection load='7ca1' size='340' side='right'caption='[[7ca1]], [[Resolution|resolution]] 3.60Å' 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=7CA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CA1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ca1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CA1 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=7ca1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca1 OCA], [https://pdbe.org/7ca1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ca1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ca1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ca1 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=90R:5-hydroxy-2-methylnaphthalene-1,4-dione'>90R</scene>, <scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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;'>[[6l0a|6l0a]], [[6l0b|6l0b]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">URA4, YLR420W, L9931.1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydroorotase Dihydroorotase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.3 3.5.2.3] </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=7ca1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca1 OCA], [https://pdbe.org/7ca1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ca1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ca1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ca1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway for pyrimidine nucleotides, and an attractive target for potential anticancer chemotherapy. By screening plant extracts and performing GC-MS analysis, we identified and characterized that the potent anticancer drug plumbagin (PLU), isolated from the carnivorous plant Nepenthes miranda, was a competitive inhibitor of DHOase. We also solved the complexed crystal structure of yeast DHOase with PLU (PDB entry 7CA1), to determine the binding interactions and investigate the binding modes. Mutational and structural analyses indicated the binding of PLU to DHOase through loop-in mode, and this dynamic loop may serve as a drug target. PLU exhibited cytotoxicity on the survival, migration, and proliferation of 4T1 cells and induced apoptosis. These results provide structural insights that may facilitate the development of new inhibitors targeting DHOase, for further clinical anticancer chemotherapies. | ||
| + | |||
| + | Plumbagin, a Natural Product with Potent Anticancer Activities, Binds to and Inhibits Dihydroorotase, a Key Enzyme in Pyrimidine Biosynthesis.,Guan HH, Huang YH, Lin ES, Chen CJ, Huang CY Int J Mol Sci. 2021 Jun 25;22(13). pii: ijms22136861. doi: 10.3390/ijms22136861. PMID:34202294<ref>PMID:34202294</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ca1" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Baker's yeast]] | ||
| + | [[Category: Dihydroorotase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Chen | + | [[Category: Chen, C J]] |
| - | [[Category: Guan | + | [[Category: Guan, H H]] |
| - | [[Category: Huang | + | [[Category: Huang, C Y]] |
| - | [[Category: Huang | + | [[Category: Huang, Y H]] |
| + | [[Category: Dihydropyrimidinase]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Metalloenzyme]] | ||
Revision as of 10:05, 14 July 2021
Crystal structure of dihydroorotase in complex with plumbagin from Saccharomyces cerevisiae
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