4dm9: Difference between revisions

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'''Unreleased structure'''


The entry 4dm9 is ON HOLD  until Paper Publication
==The Crystal Structure of Ubiquitin Carboxy-terminal hydrolase L1 (UCHL1) bound to a tripeptide fluoromethyl ketone Z-VAE(OMe)-FMK==
<StructureSection load='4dm9' size='340' side='right'caption='[[4dm9]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dm9]] is a 4 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=4DM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DM9 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=GME:5-O-METHYL-GLUTAMIC+ACID'>GME</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</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=4dm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dm9 OCA], [https://pdbe.org/4dm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dm9 RCSB], [https://www.ebi.ac.uk/pdbsum/4dm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dm9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/UCHL1_HUMAN UCHL1_HUMAN] Defects in UCHL1 are the cause of Parkinson disease type 5 (PARK5) [MIM:[https://omim.org/entry/613643 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.<ref>PMID:12408865</ref> <ref>PMID:9774100</ref> <ref>PMID:12705903</ref> <ref>PMID:16450370</ref>
== 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>


Authors: Davies, C.W., Chaney, J., Korbel, G., Ringe, D., Petsko, G.A., Ploegh, H., Das, C.
==See Also==
 
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
Description: The Crystal Structure of Ubiquitin Carboxy-terminal hydrolase L1 (UCHL1) bound to a tripeptide fluoromethyl ketone Z-VAE(OMe)-FMK
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chaney J]]
[[Category: Das C]]
[[Category: Davies CW]]
[[Category: Korbel G]]
[[Category: Petsko GA]]
[[Category: Ploegh H]]
[[Category: Ringe D]]

Latest revision as of 17:38, 14 March 2024

The Crystal Structure of Ubiquitin Carboxy-terminal hydrolase L1 (UCHL1) bound to a tripeptide fluoromethyl ketone Z-VAE(OMe)-FMKThe Crystal Structure of Ubiquitin Carboxy-terminal hydrolase L1 (UCHL1) bound to a tripeptide fluoromethyl ketone Z-VAE(OMe)-FMK

Structural highlights

4dm9 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.35Å
Ligands:, ,
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]

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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

4dm9, resolution 2.35Å

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