2ETL

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

Summary for 2ETL

• Entry DOI: 10.2210/pdb2etl/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase isozyme L1, CHLORIDE ION (3 entities in total)
• Functional Keywords: deubiquitinating thiol hydrolase, hydrolase, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P09936
• Total number of polymer chains: 2
• Total formula weight: 50675.41

Authors

Das, C.,Hoang, Q.Q.,Kreinbring, C.A.,Luchansky, S.J.,Meray, R.K.,Ray, S.S.,Lansbury, P.T.,Ringe, D.,Petsko, G.A. (deposition date: 2005-10-27, release date: 2006-03-28, Last modification date: 2024-04-03)

Primary citation

Das, C.,Hoang, Q.Q.,Kreinbring, C.A.,Luchansky, S.J.,Meray, R.K.,Ray, S.S.,Lansbury, P.T.,Ringe, D.,Petsko, G.A.
Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1.
Proc.Natl.Acad.Sci.USA, 103:4675-4680, 2006

PubMed Abstract: 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.

PubMed: 16537382
DOI: 10.1073/pnas.0510403103

Experimental method

X-RAY DIFFRACTION (2.4 Å)