PDBsum entry 4bm9

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protein ligands metals links
Ligase PDB id
Protein chain
301 a.a.
SO4 ×3
_ZN ×8
Waters ×87
PDB id:
Name: Ligase
Title: Structure of the autoinhibited parkin catalytic domain
Structure: E3 ubiquitin-protein ligase parkin. Chain: a. Fragment: upd and rbr domain, residues 137-465. Synonym: parkinson juvenile disease protein 2, parkinson di protein 2, parkin. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta2
2.25Å     R-factor:   0.191     R-free:   0.217
Authors: T.Wauer,D.Komander
Key ref: T.Wauer and D.Komander (2013). Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J, 32, 2099-2112. PubMed id: 23727886 DOI: 10.1038/emboj.2013.125
07-May-13     Release date:   12-Jun-13    
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Protein chain
Pfam   ArchSchema ?
O60260  (PRKN2_HUMAN) -  E3 ubiquitin-protein ligase parkin
465 a.a.
301 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.3.2.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biochemical function     ubiquitin-protein ligase activity     2 terms  


DOI no: 10.1038/emboj.2013.125 EMBO J 32:2099-2112 (2013)
PubMed id: 23727886  
Structure of the human Parkin ligase domain in an autoinhibited state.
T.Wauer, D.Komander.
Mutations in the protein Parkin are associated with Parkinson's disease (PD), the second most common neurodegenerative disease in men. Parkin is an E3 ubiquitin (Ub) ligase of the structurally uncharacterized RING-in-between-RING(IBR)-RING (RBR) family, which, in an HECT-like fashion, forms a catalytic thioester intermediate with Ub. We here report the crystal structure of human Parkin spanning the Unique Parkin domain (UPD, also annotated as RING0) and RBR domains, revealing a tightly packed structure with unanticipated domain interfaces. The UPD adopts a novel elongated Zn-binding fold, while RING2 resembles an IBR domain. Two key interactions keep Parkin in an autoinhibited conformation. A linker that connects the IBR with the RING2 over a 50-Å distance blocks the conserved E2∼Ub binding site of RING1. RING2 forms a hydrophobic interface with the UPD, burying the catalytic Cys431, which is part of a conserved catalytic triad. Opening of intra-domain interfaces activates Parkin, and enables Ub-based suicide probes to modify Cys431. The structure further reveals a putative phospho-peptide docking site in the UPD, and explains many PD-causing mutations.