8is5

Structure of an Isocytosine specific deaminase Vcz with close state

spinqualitylabelsall models 8is5, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8is5 is a 2 chain structure with sequence from Obesumbacterium proteus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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