7uxd
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of APOBEC3G Catalytic domain complex with ssDNA containing 2'-deoxy Zebularine.== | |
| + | <StructureSection load='7uxd' size='340' side='right'caption='[[7uxd]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7uxd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UXD 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]] 1.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DDN:3,4-DIHYDRO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>DDN</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=7uxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uxd OCA], [https://pdbe.org/7uxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uxd RCSB], [https://www.ebi.ac.uk/pdbsum/7uxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uxd ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ABC3G_HUMAN ABC3G_HUMAN] DNA deaminase (cytidine deaminase) that mediates a form of innate resistance to retroviral infections (at least to HIV-1 infection) by triggering G-to-A hypermutation in the newly synthesized viral DNA. The replacements C-to-U in the minus strand DNA of HIV-1 during reverse transcription, leads to G-to-A transitions in the plus strand. The inhibition of viral replication is either due to the degradation of the minus strand before its integration or to the lethality of the hypermutations. Modification of both DNA strands is not excluded. This antiviral activity is neutralized by the virion infectivity factor (VIF), that prevents the incorporation of APOBEC3G into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome. May also prevent the transposition of a subset of retroelements. Binds a variety of RNAs, but does not display detectable APOB, NF1 and NAT1 mRNA editing.<ref>PMID:14557625</ref> <ref>PMID:12167863</ref> <ref>PMID:12808466</ref> <ref>PMID:12809610</ref> <ref>PMID:12808465</ref> <ref>PMID:12859895</ref> <ref>PMID:12970355</ref> <ref>PMID:14528300</ref> <ref>PMID:15031497</ref> <ref>PMID:16527742</ref> <ref>PMID:21123384</ref> <ref>PMID:18288108</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | APOBEC3 proteins (A3s) are enzymes that catalyze the deamination of cytidine to uridine in single-stranded DNA (ssDNA) substrates, thus playing a key role in innate antiviral immunity. However, the APOBEC3 family has also been linked to many mutational signatures in cancer cells, which has led to an intense interest to develop inhibitors of A3's catalytic activity as therapeutics as well as tools to study A3's biochemistry, structure, and cellular function. Recent studies have shown that ssDNA containing 2'-deoxy-zebularine (dZ-ssDNA) is an inhibitor of A3s such as A3A, A3B, and A3G, although the atomic determinants of this activity have remained unknown. To fill this knowledge gap, we determined a 1.5 A resolution structure of a dZ-ssDNA inhibitor bound to active A3G. The crystal structure revealed that the activated dZ-H(2)O mimics the transition state by coordinating the active site Zn(2+) and engaging in additional stabilizing interactions, such as the one with the catalytic residue E259. Therefore, this structure allowed us to capture a snapshot of the A3's transition state and suggests that developing transition-state mimicking inhibitors may provide a new opportunity to design more targeted molecules for A3s in the future. | ||
| - | + | Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state.,Maiti A, Hedger AK, Myint W, Balachandran V, Watts JK, Schiffer CA, Matsuo H Nat Commun. 2022 Nov 19;13(1):7117. doi: 10.1038/s41467-022-34752-1. PMID:36402773<ref>PMID:36402773</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7uxd" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Maiti A]] | ||
| + | [[Category: Matsuo H]] | ||
Current revision
Crystal structure of APOBEC3G Catalytic domain complex with ssDNA containing 2'-deoxy Zebularine.
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