View source for 5sww


==Crystal Structure of Human APOBEC3A complexed with ssDNA==
<StructureSection load='5sww' size='340' side='right'caption='[[5sww]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5sww]] is a 8 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=5SWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SWW 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]] 3.151&#8491;</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=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=5sww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sww OCA], [https://pdbe.org/5sww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sww RCSB], [https://www.ebi.ac.uk/pdbsum/5sww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sww ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
APOBEC-catalyzed cytosine-to-uracil deamination of single-stranded DNA (ssDNA) has beneficial functions in immunity and detrimental effects in cancer. APOBEC enzymes have intrinsic dinucleotide specificities that impart hallmark mutation signatures. Although numerous structures have been solved, mechanisms for global ssDNA recognition and local target-sequence selection remain unclear. Here we report crystal structures of human APOBEC3A and a chimera of human APOBEC3B and APOBEC3A bound to ssDNA at 3.1-A and 1.7-A resolution, respectively. These structures reveal a U-shaped DNA conformation, with the specificity-conferring -1 thymine flipped out and the target cytosine inserted deep into the zinc-coordinating active site pocket. The -1 thymine base fits into a groove between flexible loops and makes direct hydrogen bonds with the protein, accounting for the strong 5'-TC preference. These findings explain both conserved and unique properties among APOBEC family members, and they provide a basis for the rational design of inhibitors to impede the evolvability of viruses and tumors.

Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B.,Shi K, Carpenter MA, Banerjee S, Shaban NM, Kurahashi K, Salamango DJ, McCann JL, Starrett GJ, Duffy JV, Demir O, Amaro RE, Harki DA, Harris RS, Aihara H Nat Struct Mol Biol. 2016 Dec 19. doi: 10.1038/nsmb.3344. PMID:27991903<ref>PMID:27991903</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5sww" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aihara H]]
[[Category: Banerjee S]]
[[Category: Kurahashi K]]
[[Category: Shi K]]