View source for 9ava


==Co-crystal structure of human TREX1 in complex with an inhibitor==
<StructureSection load='9ava' size='340' side='right'caption='[[9ava]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ava]] is a 12 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=9AVA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9AVA 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AG1:(2R)-2-[(5R,6S,8R,9aS)-8-amino-1-oxo-5-(2-phenylethyl)hexahydro-1H-pyrrolo[1,2-a][1,4]diazepin-2(3H)-yl]-N-[(3,4-dichlorophenyl)methyl]-4-methylpentanamide'>A1AG1</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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=9ava FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ava OCA], [https://pdbe.org/9ava PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ava RCSB], [https://www.ebi.ac.uk/pdbsum/9ava PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ava ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN] Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations;Familial Chilblain lupus;Systemic lupus erythematosus;Aicardi-Goutieres syndrome. The disease is caused by variants affecting the gene represented in this entry.  Disease susceptibility is associated with variants affecting the gene represented in this entry. Enhanced immune sensing of oxidized DNA may be involved in the phototoxicity experienced by SLE patients. Exposure to UV-light produces DNA oxidative damage. Oxidized DNA being a poor TREX1 substrate, it accumulates in skin, leading to enhanced auto-immune reactivity and eventually skin lesions (PubMed:23993650).<ref>PMID:23993650</ref>   The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN] Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Prevents cell-intrinsic initiation of autoimmunity (PubMed:10391904, PubMed:10393201, PubMed:17293595). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements (PubMed:10391904, PubMed:10393201, PubMed:17293595). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation (PubMed:33476576). Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation (PubMed:33476576). Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon (PubMed:33476576). Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates (PubMed:18045533). Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 (PubMed:16818237). NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (PubMed:16818237).<ref>PMID:10391904</ref> <ref>PMID:10393201</ref> <ref>PMID:16818237</ref> <ref>PMID:17293595</ref> <ref>PMID:18045533</ref> <ref>PMID:23993650</ref> <ref>PMID:33476576</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ackloo S]]
[[Category: Arrowsmith CH]]
[[Category: Dehghani-Tafti S]]
[[Category: Dong A]]
[[Category: Edwards AM]]
[[Category: Halabelian L]]
[[Category: Li Y]]
[[Category: Xu J]]