PDBsum entry 2etl

Hydrolase, ligase

PDB id: 2etl

Contents

Protein chain

223 a.a. *

Metals

_CL ×4

Waters ×107

* Residue conservation analysis

PDB id:

2etl

Name:

Hydrolase, ligase

Title:

Crystal structure of ubiquitin carboxy-terminal hydrolase l1 (uch-l1)

Structure:

Ubiquitin carboxyl-terminal hydrolase isozyme l1. Chain: a, b. Synonym: uch-l1, ubiquitin thiolesterase l1, neuron cytoplasmic protein 9.5, pgp 9.5, pgp9.5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: uchl1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.40Å R-factor: 0.223 R-free: 0.274

Authors:

C.Das,Q.Q.Hoang,C.A.Kreinbring,S.J.Luchansky,R.K.Meray,S.S.Ray, P.T.Lansbury,D.Ringe,G.A.Petsko

Key ref:

C.Das et al. (2006). Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. Proc Natl Acad Sci U S A, 103, 4675-4680. PubMed id: 16537382 DOI: 10.1073/pnas.0510403103

Date:

27-Oct-05 Release date: 28-Mar-06

Protein chains

P09936  (UCHL1_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase isozyme L1 from Homo sapiens

Seq: 223 a.a.

Struc: 223 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.19.12 - ubiquitinyl hydrolase 1.
• Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

DOI no: 10.1073/pnas.0510403103

Proc Natl Acad Sci U S A 103:4675-4680 (2006)

PubMed id: 16537382

Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1.

C.Das, Q.Q.Hoang, C.A.Kreinbring, S.J.Luchansky, R.K.Meray, S.S.Ray, P.T.Lansbury, D.Ringe, G.A.Petsko.

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.

Selected figure(s)

Figure 3.
Fig. 3. Molecular surface of UCH-L1. Conserved acidic side chains are colored red, basic side chains are colored blue, polar side chains are colored orange, and all nonconserved residues according to Fig. 1 are colored gray. B is related to A by a rotation of 50° about the y axis. D is related to C by a rotation of 90° about the x axis.

Figure 4.
Fig. 4. Structure of UCH-L1's active site. Backbone atoms are presented as semitransparent orange ribbons. Atoms of interest are presented as sticks and spheres. Oxygens, red; nitrogen, blue; sulfur, gold; chlorine, green. Distances between two atoms are presented with gray dashed lines. Electron density (contoured at 1.5 ) is shown as gray lines.

Figures were selected by an automated process.