7zm0
From Proteopedia
(Difference between revisions)
| Line 5: | Line 5: | ||
<table><tr><td colspan='2'>[[7zm0]] is a 10 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=7ZM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZM0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zm0]] is a 10 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=7ZM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZM0 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]] 2.24Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JMF:( | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JMF:(3~{S})-1-(iminomethyl)-~{N}-[1-[4-(pent-4-ynylcarbamoyl)phenyl]imidazol-4-yl]pyrrolidine-3-carboxamide'>JMF</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=7zm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zm0 OCA], [https://pdbe.org/7zm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zm0 RCSB], [https://www.ebi.ac.uk/pdbsum/7zm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zm0 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=7zm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zm0 OCA], [https://pdbe.org/7zm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zm0 RCSB], [https://www.ebi.ac.uk/pdbsum/7zm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zm0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 12: | Line 12: | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/UCHL1_HUMAN UCHL1_HUMAN] Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.<ref>PMID:9790970</ref> <ref>PMID:12408865</ref> <ref>PMID:18411255</ref> | [https://www.uniprot.org/uniprot/UCHL1_HUMAN UCHL1_HUMAN] Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.<ref>PMID:9790970</ref> <ref>PMID:12408865</ref> <ref>PMID:18411255</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Ubiquitination regulates protein homeostasis and is tightly controlled by deubiquitinases (DUBs). Loss of the DUB UCHL1 leads to neurodegeneration, and its dysregulation promotes cancer metastasis and invasiveness. Small molecule probes for UCHL1 and DUBs in general could help investigate their function, yet specific inhibitors and structural information are rare. Here we report the potent and non-toxic chemogenomic pair of activity-based probes GK13S and GK16S for UCHL1. Biochemical characterization of GK13S demonstrates its stereoselective inhibition of cellular UCHL1. The crystal structure of UCHL1 in complex with GK13S shows the enzyme locked in a hybrid conformation of apo and Ubiquitin-bound states, which underlies its UCHL1-specificity within the UCH DUB family. Phenocopying a reported inactivating mutation of UCHL1 in mice, GK13S, but not GK16S, leads to reduced levels of monoubiquitin in a human glioblastoma cell line. Collectively, we introduce a set of structurally characterized, chemogenomic probes suitable for the cellular investigation of UCHL1. | ||
| + | |||
| + | Structural basis for specific inhibition of the deubiquitinase UCHL1.,Grethe C, Schmidt M, Kipka GM, O'Dea R, Gallant K, Janning P, Gersch M Nat Commun. 2022 Oct 10;13(1):5950. doi: 10.1038/s41467-022-33559-4. PMID:36216817<ref>PMID:36216817</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7zm0" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Structure of UCHL1 in complex with GK13S inhibitor
| |||||||||||
