8is4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of an Isocytosine specific deaminase Vcz in complexed with 5-FU== | |
| + | <StructureSection load='8is4' size='340' side='right'caption='[[8is4]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8is4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Obesumbacterium_proteus Obesumbacterium proteus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IS4 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]] 1.9Å</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=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8is4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8is4 OCA], [https://pdbe.org/8is4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8is4 RCSB], [https://www.ebi.ac.uk/pdbsum/8is4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8is4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction. We also captured the substrate-induced conformational changes of VCZ, then proposed the conjectural reaction procedures of VCZ for converting the IC into the uracil. Moreover, we evaluated the therapeutic effect of wildtype or the mutated VCZ protein in the colorectal cancer cell lines. Our studies will shed light on optimizing the ICD/5-FIC pairs by modifying either the enzyme or the prodrug based on the structural observations, thereby improving the possibility of applying the ICD/5-FIC pair in clinical trials. | ||
| - | + | Structural characterization of an isocytosine-specific deaminase VCZ reveals its application potential in the anti-cancer therapy.,Guo W, Li X, Fan J, Li H, Wen Y, Meng C, Chen H, Zhao Z, Zhang Y, Du Y, Wu B iScience. 2023 Aug 18;26(9):107672. doi: 10.1016/j.isci.2023.107672. eCollection , 2023 Sep 15. PMID:37680460<ref>PMID:37680460</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8is4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Obesumbacterium proteus]] | ||
| + | [[Category: Guo WT]] | ||
| + | [[Category: Li XJ]] | ||
| + | [[Category: Wu BX]] | ||
Current revision
Structure of an Isocytosine specific deaminase Vcz in complexed with 5-FU
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