1xd3

From Proteopedia

(Difference between revisions)

Revision as of 07:16, 18 April 2018

Crystal structure of UCHL3-UbVME complex

Structural highlights

1xd3 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1cmx, 1ubq, 1uch
Activity:	Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Ubiquitin C-terminal hydrolases (UCHs) comprise a family of small ubiquitin-specific proteases of uncertain function. Although no cellular substrates have been identified for UCHs, their highly tissue-specific expression patterns and the association of UCH-L1 mutations with human disease strongly suggest a critical role. The structure of the yeast UCH Yuh1-ubiquitin aldehyde complex identified an active site crossover loop predicted to limit the size of suitable substrates. We report the 1.45 A resolution crystal structure of human UCH-L3 in complex with the inhibitor ubiquitin vinylmethylester, an inhibitor that forms a covalent adduct with the active site cysteine of ubiquitin-specific proteases. This structure confirms the predicted mechanism of the inhibitor and allows the direct comparison of a UCH family enzyme in the free and ligand-bound state. We also show the efficient hydrolysis by human UCH-L3 of a 13-residue peptide in isopeptide linkage with ubiquitin, consistent with considerable flexibility in UCH substrate size. We propose a model for the catalytic cycle of UCH family members which accounts for the hydrolysis of larger ubiquitin conjugates.

Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate.,Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R J Biol Chem. 2005 Jan 14;280(2):1512-20. Epub 2004 Nov 5. PMID:15531586^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science. 1989 Nov 3;246(4930):670-3. PMID:2530630
↑ Wada H, Kito K, Caskey LS, Yeh ET, Kamitani T. Cleavage of the C-terminus of NEDD8 by UCH-L3. Biochem Biophys Res Commun. 1998 Oct 29;251(3):688-92. PMID:9790970 doi:S0006-291X(98)99532-8
↑ Setsuie R, Sakurai M, Sakaguchi Y, Wada K. Ubiquitin dimers control the hydrolase activity of UCH-L3. Neurochem Int. 2009 May-Jun;54(5-6):314-21. doi: 10.1016/j.neuint.2008.12.013., Epub 2008 Dec 25. PMID:19154770 doi:http://dx.doi.org/10.1016/j.neuint.2008.12.013
↑ Dennissen FJ, Kholod N, Hermes DJ, Kemmerling N, Steinbusch HW, Dantuma NP, van Leeuwen FW. Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3). FEBS Lett. 2011 Aug 19;585(16):2568-74. doi: 10.1016/j.febslet.2011.06.037. Epub , 2011 Jul 6. PMID:21762696 doi:http://dx.doi.org/10.1016/j.febslet.2011.06.037
↑ Iphofer A, Kummer A, Nimtz M, Ritter A, Arnold T, Frank R, van den Heuvel J, Kessler BM, Jansch L, Franke R. Profiling ubiquitin linkage specificities of deubiquitinating enzymes with branched ubiquitin isopeptide probes. Chembiochem. 2012 Jul 9;13(10):1416-20. doi: 10.1002/cbic.201200261. Epub 2012, Jun 11. PMID:22689415 doi:10.1002/cbic.201200261
↑ Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R. Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate. J Biol Chem. 2005 Jan 14;280(2):1512-20. Epub 2004 Nov 5. PMID:15531586 doi:http://dx.doi.org/10.1074/jbc.M410770200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xd3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of UCHL3-UbVME complex==
 <StructureSection load='1xd3' size='340' side='right' caption='[[1xd3]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cmx|1cmx]], [[1ubq|1ubq]], [[1uch|1uch]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>
-<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=1xd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xd3 OCA], [http://pdbe.org/1xd3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xd3 RCSB], [http://www.ebi.ac.uk/pdbsum/1xd3 PDBsum]</span></td></tr>
+<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=1xd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xd3 OCA], [http://pdbe.org/1xd3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xd3 RCSB], [http://www.ebi.ac.uk/pdbsum/1xd3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xd3 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xd/1xd3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xd/1xd3_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1xd3

From Proteopedia

Revision as of 07:16, 18 April 2018

Crystal structure of UCHL3-UbVME complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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