View source for 7yv4


==Crystal structure of human UCHL3 in complex with Farrerol==
<StructureSection load='7yv4' size='340' side='right'caption='[[7yv4]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7yv4]] is a 1 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=7YV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YV4 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]] 1.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JXY:(2~{S})-2-(4-hydroxyphenyl)-6,8-dimethyl-5,7-bis(oxidanyl)-2,3-dihydrochromen-4-one'>JXY</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=7yv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yv4 OCA], [https://pdbe.org/7yv4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yv4 RCSB], [https://www.ebi.ac.uk/pdbsum/7yv4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yv4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UCHL3_HUMAN UCHL3_HUMAN] Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.<ref>PMID:2530630</ref> <ref>PMID:9790970</ref> <ref>PMID:19154770</ref> <ref>PMID:21762696</ref> <ref>PMID:22689415</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Farrerol, a natural flavanone, promotes homologous recombination (HR) repair to improve genome-editing efficiency, but the specific protein that farrerol directly targets to regulate HR repair and the underlying molecular mechanisms have not been determined. Here, we find that the deubiquitinase UCHL3 is the direct target of farrerol. Mechanistically, farrerol enhanced the deubiquitinase activity of UCHL3 to promote RAD51 deubiquitination, thereby improving HR repair. Importantly, we find that embryos of somatic cell nuclear transfer (SCNT) exhibited defective HR repair, increased genomic instability and aneuploidy, and that the farrerol treatment post nuclear transfer enhances HR repair, restores transcriptional and epigenetic network, and promotes SCNT embryo development. Ablating UCHL3 significantly attenuates farrerol-mediated stimulation in HR and SCNT embryo development. In summary, we identify farrerol as an activator of the deubiquitinase UCHL3, highlighted the importance of HR and epigenetic changes in SCNT reprogramming and provide a feasible method to promote SCNT efficiency.

Farrerol directly activates the deubiqutinase UCHL3 to promote DNA repair and reprogramming when mediated by somatic cell nuclear transfer.,Zhang W, Wang M, Song Z, Fu Q, Chen J, Zhang W, Gao S, Sun X, Yang G, Zhang Q, Yang J, Tang H, Wang H, Kou X, Wang H, Mao Z, Xu X, Gao S, Jiang Y Nat Commun. 2023 Apr 3;14(1):1838. doi: 10.1038/s41467-023-37576-9. PMID:37012254<ref>PMID:37012254</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7yv4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mao ZY]]
[[Category: Xu XJ]]
[[Category: Zhang WT]]