View source for 3vow


==Crystal Structure of the Human APOBEC3C having HIV-1 Vif-binding Interface==
<StructureSection load='3vow' size='340' side='right'caption='[[3vow]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3vow]] is a 2 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=3VOW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VOW 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]] 2.15&#8491;</td></tr>
<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=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=3vow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vow OCA], [https://pdbe.org/3vow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vow RCSB], [https://www.ebi.ac.uk/pdbsum/3vow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vow ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ABC3C_HUMAN ABC3C_HUMAN] DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single-or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV), herpes simplex virus 1 (HHV-1) and Epstein-Barr virus (EBV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.<ref>PMID:12859895</ref> <ref>PMID:15466872</ref> <ref>PMID:16527742</ref> <ref>PMID:20062055</ref> <ref>PMID:21496894</ref> <ref>PMID:21632763</ref> 
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== Publication Abstract from PubMed ==
The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3, referred to as A3) proteins are cellular cytidine deaminases that potently restrict retrovirus replication. However, HIV-1 viral infectivity factor (Vif) counteracts the antiviral activity of most A3 proteins by targeting them for proteasomal degradation. To date, the structure of an A3 protein containing a Vif-binding interface has not been solved. Here, we report a high-resolution crystal structure of APOBEC3C and identify the HIV-1 Vif-interaction interface. Extensive structure-guided mutagenesis revealed the role of a shallow cavity composed of hydrophobic or negatively charged residues between the alpha2 and alpha3 helices. This region is distant from the DPD motif (residues 128-130) of APOBEC3G that participates in HIV-1 Vif interaction. These findings provide insight into Vif-A3 interactions and could lead to the development of new pharmacologic anti-HIV-1 compounds.

The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.,Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, Yokomaku Y, Yamane T, Watanabe N, Suzuki A, Sugiura W, Iwatani Y Nat Struct Mol Biol. 2012 Sep 23;19(10):1005-10. doi: 10.1038/nsmb.2378. Epub, 2012 Sep 23. PMID:23001005<ref>PMID:23001005</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3vow" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Iwatani Y]]
[[Category: Kitamura S]]
[[Category: Suzuki A]]
[[Category: Watanabe N]]