8fik

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'''Unreleased structure'''
 
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The entry 8fik is ON HOLD until Paper Publication
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==APOBEC3A E72A inactive mutant in complex with ATTC-hairpin DNA substrate==
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<StructureSection load='8fik' size='340' side='right'caption='[[8fik]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8fik]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FIK FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.912&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8fik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fik OCA], [https://pdbe.org/8fik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fik RCSB], [https://www.ebi.ac.uk/pdbsum/8fik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fik ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ABC3A_HUMAN ABC3A_HUMAN] DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno-associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.<ref>PMID:10469298</ref> <ref>PMID:12859895</ref> <ref>PMID:16527742</ref> <ref>PMID:19461882</ref> <ref>PMID:20615867</ref> <ref>PMID:20062055</ref> <ref>PMID:21496894</ref> <ref>PMID:21460793</ref> <ref>PMID:21123384</ref> <ref>PMID:21368204</ref> <ref>PMID:22896697</ref> <ref>PMID:22457529</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The normally antiviral enzyme APOBEC3A is an endogenous mutagen in human cancer. Its single-stranded DNA C-to-U editing activity results in multiple mutagenic outcomes including signature single-base substitution mutations (isolated and clustered), DNA breakage, and larger-scale chromosomal aberrations. APOBEC3A inhibitors may therefore comprise a unique class of anti-cancer agents that work by blocking mutagenesis, slowing tumor evolvability, and preventing detrimental outcomes such as drug resistance and metastasis. Here we reveal the structural basis of competitive inhibition of wildtype APOBEC3A by hairpin DNA bearing 2'-deoxy-5-fluorozebularine in place of the cytidine in the TC substrate motif that is part of a 3-nucleotide loop. In addition, the structural basis of APOBEC3A's preference for YTCD motifs (Y = T, C; D = A, G, T) is explained. The nuclease-resistant phosphorothioated derivatives of these inhibitors have nanomolar potency in vitro and block APOBEC3A activity in human cells. These inhibitors may be useful probes for studying APOBEC3A activity in cellular systems and leading toward, potentially as conjuvants, next-generation, combinatorial anti-mutator and anti-cancer therapies.
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Authors: Harjes, S., Jameson, G.B., Harjes, E., Filichev, V.V., Kurup, H.M.
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Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A.,Harjes S, Kurup HM, Rieffer AE, Bayarjargal M, Filitcheva J, Su Y, Hale TK, Filichev VV, Harjes E, Harris RS, Jameson GB Nat Commun. 2023 Oct 11;14(1):6382. doi: 10.1038/s41467-023-42174-w. PMID:37821454<ref>PMID:37821454</ref>
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Description: APOBEC3A E72A inactive mutant in complex with ATTC-hairpin DNA substrate
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Kurup, H.M]]
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<div class="pdbe-citations 8fik" style="background-color:#fffaf0;"></div>
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[[Category: Jameson, G.B]]
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== References ==
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[[Category: Harjes, E]]
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<references/>
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[[Category: Filichev, V.V]]
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__TOC__
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[[Category: Harjes, S]]
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Filichev VV]]
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[[Category: Harjes E]]
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[[Category: Harjes S]]
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[[Category: Jameson GB]]
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[[Category: Kurup HM]]

Current revision

APOBEC3A E72A inactive mutant in complex with ATTC-hairpin DNA substrate

PDB ID 8fik

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