4ndi

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{{STRUCTURE_4ndi| PDB=4ndi | SCENE= }}
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==Human Aprataxin (Aptx) AOA1 variant K197Q bound to RNA-DNA, AMP, and Zn - product complex==
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===Human Aprataxin (Aptx) AOA1 variant K197Q bound to RNA-DNA, AMP, and Zn - product complex===
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<StructureSection load='4ndi' size='340' side='right' caption='[[4ndi]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24362567}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4ndi]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NDI FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3szq|3szq]], [[4ndf|4ndf]], [[4ndg|4ndg]], [[4ndh|4ndh]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APTX, AXA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ndi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ndi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ndi RCSB], [http://www.ebi.ac.uk/pdbsum/4ndi PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/APTX_HUMAN APTX_HUMAN]] Defects in APTX are the cause of ataxia-oculomotor apraxia syndrome (AOA) [MIM:[http://omim.org/entry/208920 208920]]. AOA is an autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.<ref>PMID:11586299</ref> <ref>PMID:11586300</ref> <ref>PMID:12196655</ref> <ref>PMID:12629250</ref> <ref>PMID:14506070</ref> <ref>PMID:15852392</ref> <ref>PMID:15699391</ref>
[[http://www.uniprot.org/uniprot/APTX_HUMAN APTX_HUMAN]] Defects in APTX are the cause of ataxia-oculomotor apraxia syndrome (AOA) [MIM:[http://omim.org/entry/208920 208920]]. AOA is an autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.<ref>PMID:11586299</ref> <ref>PMID:11586300</ref> <ref>PMID:12196655</ref> <ref>PMID:12629250</ref> <ref>PMID:14506070</ref> <ref>PMID:15852392</ref> <ref>PMID:15699391</ref>
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== Function ==
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==Function==
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[[http://www.uniprot.org/uniprot/APTX_HUMAN APTX_HUMAN]] DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity.<ref>PMID:14755728</ref> <ref>PMID:15044383</ref> <ref>PMID:16547001</ref> <ref>PMID:16964241</ref> <ref>PMID:17276982</ref>
[[http://www.uniprot.org/uniprot/APTX_HUMAN APTX_HUMAN]] DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity.<ref>PMID:14755728</ref> <ref>PMID:15044383</ref> <ref>PMID:16547001</ref> <ref>PMID:16964241</ref> <ref>PMID:17276982</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions. Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-Zn complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease.
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==About this Structure==
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Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.,Tumbale P, Williams JS, Schellenberg MJ, Kunkel TA, Williams RS Nature. 2013 Dec 22. doi: 10.1038/nature12824. PMID:24362567<ref>PMID:24362567</ref>
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[[4ndi]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NDI OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024362567</ref><references group="xtra"/><references/>
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</div>
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[[Category: Schellenberg, M J.]]
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== References ==
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[[Category: Tumbale, P S.]]
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<references/>
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[[Category: Williams, R S.]]
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__TOC__
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</StructureSection>
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[[Category: Human]]
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[[Category: Schellenberg, M J]]
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[[Category: Tumbale, P S]]
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[[Category: Williams, R S]]
[[Category: 5'-dna end processing]]
[[Category: 5'-dna end processing]]
[[Category: 5'-dna end recognition]]
[[Category: 5'-dna end recognition]]

Revision as of 09:47, 5 January 2015

Human Aprataxin (Aptx) AOA1 variant K197Q bound to RNA-DNA, AMP, and Zn - product complex

4ndi, resolution 1.90Å

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