PDBsum entry 3irt

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protein metals Protein-protein interface(s) links
Hydrolase, ligase PDB id
Jmol PyMol
Protein chain
223 a.a. *
_CL ×2
Waters ×35
* Residue conservation analysis
PDB id:
Name: Hydrolase, ligase
Title: Crystal structure of the i93m mutant of ubiquitin carboxy-te hydrolase l1
Structure: Ubiquitin carboxyl-terminal hydrolase isozyme l1. Chain: a, b. Synonym: uch-l1, ubiquitin thioesterase l1, neuron cytoplas protein 9.5, pgp 9.5, pgp9.5. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pgp9.5, uchl1. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.80Å     R-factor:   0.213     R-free:   0.254
Authors: C.W.Davies,T.K.Maiti,C.Das
Key ref: D.A.Boudreaux et al. (2010). Ubiquitin vinyl methyl ester binding orients the misaligned active site of the ubiquitin hydrolase UCHL1 into productive conformation. Proc Natl Acad Sci U S A, 107, 9117-9122. PubMed id: 20439756
24-Aug-09     Release date:   09-Jun-10    
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Protein chains
Pfam   ArchSchema ?
P09936  (UCHL1_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase isozyme L1
223 a.a.
223 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Ubiquitinyl hydrolase 1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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).
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     neuron projection terminus   14 terms 
  Biological process     response to ischemia   16 terms 
  Biochemical function     protein binding     12 terms  


Proc Natl Acad Sci U S A 107:9117-9122 (2010)
PubMed id: 20439756  
Ubiquitin vinyl methyl ester binding orients the misaligned active site of the ubiquitin hydrolase UCHL1 into productive conformation.
D.A.Boudreaux, T.K.Maiti, C.W.Davies, C.Das.
Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a Parkinson disease-associated, putative cysteine protease found abundantly and selectively expressed in neurons. The crystal structure of apo UCHL1 showed that the active-site residues are not aligned in a canonical form, with the nucleophilic cysteine being 7.7 A from the general base histidine, an arrangement consistent with an inactive form of the enzyme. Here we report the crystal structures of the wild type and two Parkinson disease-associated variants of the enzyme, S18Y and I93M, bound to a ubiquitin-based suicide substrate, ubiquitin vinyl methyl ester. These structures reveal that ubiquitin vinyl methyl ester binds primarily at two sites on the enzyme, with its carboxy terminus at the active site and with its amino-terminal beta-hairpin at the distal site-a surface-exposed hydrophobic crevice 17 A away from the active site. Binding at the distal site initiates a cascade of side-chain movements in the enzyme that starts at a highly conserved, surface-exposed phenylalanine and is relayed to the active site resulting in the reorientation and proximal placement of the general base within 4 A of the catalytic cysteine, an arrangement found in productive cysteine proteases. Mutation of the distal-site, surface-exposed phenylalanine to alanine reduces ubiquitin binding and severely impairs the catalytic activity of the enzyme. These results suggest that the activity of UCHL1 may be regulated by its own substrate.