This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2etl

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:28, 18 October 2017

Crystal Structure of Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1)

Structural highlights

2etl is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	UCHL1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[UCHL1_HUMAN] Defects in UCHL1 are the cause of Parkinson disease type 5 (PARK5) [MIM:613643]; also known as Parkinson disease autosomal dominant 5. PARK5 is a complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.^[1] ^[2] ^[3] ^[4]

Function

[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.^[5] ^[6] ^[7]

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

The ubiquitin C-terminal hydrolase UCH-L1 (PGP9.5) comprises >1% of total brain protein but is almost absent from other tissues [Wilkinson, K. D., et al. (1989) Science 246, 670-673]. Mutations in the UCH-L1 gene have been reported to be linked to susceptibility to and protection from Parkinson's disease [Leroy, E., et al. (1998) Nature 395, 451-452; Maraganore, D. M., et al. (1999) Neurology 53, 1858-1860]. Abnormal overexpression of UCH-L1 has been shown to correlate with several forms of cancer [Hibi, K., et al. (1998) Cancer Res. 58, 5690-5694]. Because the amino acid sequence of UCH-L1 is similar to that of other ubiquitin C-terminal hydrolases, including the ubiquitously expressed UCH-L3, which appear to be unconnected to neurodegenerative disease, the structure of UCH-L1 and the effects of disease associated mutations on the structure and function are of considerable importance. We have determined the three-dimensional structure of human UCH-L1 at 2.4-A resolution by x-ray crystallography. The overall fold resembles that of other ubiquitin hydrolases, including UCH-L3, but there are a number of significant differences. In particular, the geometry of the catalytic residues in the active site of UCH-L1 is distorted in such a way that the hydrolytic activity would appear to be impossible without substrate induced conformational rearrangements.

Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1.,Das C, Hoang QQ, Kreinbring CA, Luchansky SJ, Meray RK, Ray SS, Lansbury PT, Ringe D, Petsko GA Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4675-80. Epub 2006 Mar 13. PMID:16537382^[8]

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

References

↑ Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002 Oct 18;111(2):209-18. PMID:12408865
↑ Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH. The ubiquitin pathway in Parkinson's disease. Nature. 1998 Oct 1;395(6701):451-2. PMID:9774100 doi:10.1038/26652
↑ Nishikawa K, Li H, Kawamura R, Osaka H, Wang YL, Hara Y, Hirokawa T, Manago Y, Amano T, Noda M, Aoki S, Wada K. Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. Biochem Biophys Res Commun. 2003 Apr 25;304(1):176-83. PMID:12705903
↑ Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, Muqit MM, Foltynie T, Barker R, Bhatia KP, Quinn NP, Lees AJ, Gibson JM, Holton JL, Revesz T, Goldstein DB, Wood NW. UCHL-1 is not a Parkinson's disease susceptibility gene. Ann Neurol. 2006 Apr;59(4):627-33. PMID:16450370 doi:10.1002/ana.20757
↑ 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
↑ Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002 Oct 18;111(2):209-18. PMID:12408865
↑ Kyratzi E, Pavlaki M, Stefanis L. The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells. Hum Mol Genet. 2008 Jul 15;17(14):2160-71. doi: 10.1093/hmg/ddn115. Epub 2008 Apr, 14. PMID:18411255 doi:10.1093/hmg/ddn115
↑ Das C, Hoang QQ, Kreinbring CA, Luchansky SJ, Meray RK, Ray SS, Lansbury PT, Ringe D, Petsko GA. Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4675-80. Epub 2006 Mar 13. PMID:16537382

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2etl"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1)==
 <StructureSection load='2etl' size='340' side='right' caption='[[2etl]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UCHL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2etl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2etl OCA], [http://pdbe.org/2etl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2etl RCSB], [http://www.ebi.ac.uk/pdbsum/2etl 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=2etl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2etl OCA], [http://pdbe.org/2etl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2etl RCSB], [http://www.ebi.ac.uk/pdbsum/2etl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2etl ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 2etl" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Thioesterase|Thioesterase]]
 == References ==
 <references/>

2etl

From Proteopedia

Revision as of 07:28, 18 October 2017

Crystal Structure of Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1)

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox