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3u3y

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Current revision (10:16, 1 March 2024) (edit) (undo)
 
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<StructureSection load='3u3y' size='340' side='right'caption='[[3u3y]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
<StructureSection load='3u3y' size='340' side='right'caption='[[3u3y]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3u3y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U3Y FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3u3y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U3Y FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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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]] 2.28&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trex1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Exodeoxyribonuclease_III Exodeoxyribonuclease III], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.11.2 3.1.11.2] </span></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=3u3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u3y OCA], [https://pdbe.org/3u3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u3y RCSB], [https://www.ebi.ac.uk/pdbsum/3u3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u3y ProSAT]</span></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=3u3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u3y OCA], [https://pdbe.org/3u3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u3y RCSB], [https://www.ebi.ac.uk/pdbsum/3u3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u3y ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/TREX1_MOUSE TREX1_MOUSE]] Exonuclease with a preference for double stranded DNA with mismatched 3' termini. May play a role in DNA repair.<ref>PMID:10391904</ref> <ref>PMID:11279105</ref>
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[https://www.uniprot.org/uniprot/TREX1_MOUSE TREX1_MOUSE] Exonuclease with a preference for double stranded DNA with mismatched 3' termini. May play a role in DNA repair.<ref>PMID:10391904</ref> <ref>PMID:11279105</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mutations within the human TREX1 3' exonuclease are associated with Aicardi-Goutieres Syndrome (AGS) and familial chilblain lupus (FCL). Both AGS and FCL are autoimmune diseases that result in increased levels of interferon alpha and circulating antibodies to DNA. TREX1 is a member of the endoplasmic reticulum (ER)-associated SET complex and participates in granzyme A-mediated cell death to degrade nicked genomic DNA. The loss of TREX1 activity may result in the accumulation of double-stranded DNA (dsDNA) degradation intermediates that trigger autoimmune activation. The X-ray crystal structures of the TREX1 wt apoprotein, the dominant D200H, D200N and D18N homodimer mutants derived from AGS and FCL patients, as well as the recessive V201D homodimer mutant have been determined. The structures of the D200H and D200N mutant proteins reveal the enzyme has lost coordination of one of the active site metals, and the catalytic histidine (H195) is trapped in a conformation pointing away from the active site. The TREX1 D18N and V201D mutants are able to bind both metals in the active site, but with inter-metal distances that are larger than optimal for catalysis. Additionally, all of the mutant structures reveal a reduced mobility in the catalytic histidine, providing further explanation for the loss of catalytic activity. The structures of the mutant TREX1 proteins provide insight into the dysfunction relating to human disease. Additionally, the TREX1 apoprotein structure together with the previously determined wild type substrate and product structures allow us to propose a distinct mechanism for the TREX1 exonuclease.
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Defects in DNA degradation revealed in crystal structures of TREX1 exonuclease mutations linked to autoimmune disease.,Bailey SL, Harvey S, Perrino FW, Hollis T DNA Repair (Amst). 2011 Nov 7. PMID:22071149<ref>PMID:22071149</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3u3y" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Exodeoxyribonuclease III]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Mus musculus]]
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[[Category: Bailey, S L]]
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[[Category: Bailey SL]]
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[[Category: Harvey, S]]
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[[Category: Harvey S]]
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[[Category: Hollis, T]]
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[[Category: Hollis T]]
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[[Category: Perrino, F W]]
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[[Category: Perrino FW]]
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[[Category: 3' exonuclease]]
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[[Category: Homodimer]]
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[[Category: Hydrolase-dna complex]]
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[[Category: Rnase h fold]]
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Current revision

Mouse TREX1 D200H mutant

PDB ID 3u3y

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