PDBsum entry 4bos

Hydrolase

PDB id: 4bos

Contents

Protein chains

164 a.a.

76 a.a.

Ligands

THR-LEU-THR-GLY-LYS-THR-ILE

NO3 ×5

Metals

_MG

Waters ×231

PDB id:

4bos

Name:

Hydrolase

Title:

Structure of otud2 otu domain in complex with ubiquitin k11-linked peptide

Structure:

Ubiquitin thioesterase otu1. Chain: a, b. Fragment: otu domain, residues 147-314. Synonym: duba-8, HIV-1-induced protease 7, hin-7, hshin7, otu domain -containing protein 2, otud2. Engineered: yes. Mutation: yes. Polyubiquitin-c. Chain: c, e.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta placi.

Resolution:

2.35Å R-factor: 0.189 R-free: 0.238

Authors:

T.E.T.Mevissen,M.K.Hospenthal,P.P.Geurink,P.R.Elliott,M.Akutsu, N.Arnaudo,R.Ekkebus,Y.Kulathu,T.Wauer,F.El Oualid,S.M.V.Freund, H.Ovaa,D.Komander

Key ref:

T.E.Mevissen et al. (2013). OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell, 154, 169-184. PubMed id: 23827681 DOI: 10.1016/j.cell.2013.05.046

Date:

22-May-13 Release date: 24-Jul-13

Protein chains

Q5VVQ6  (OTU1_HUMAN) -  Ubiquitin thioesterase OTU1 from Homo sapiens

Seq: 348 a.a.

Struc: 164 a.a.*

Protein chains

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 76 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: 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: 10.1016/j.cell.2013.05.046

Cell 154:169-184 (2013)

PubMed id: 23827681

OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis.

T.E.Mevissen, M.K.Hospenthal, P.P.Geurink, P.R.Elliott, M.Akutsu, N.Arnaudo, R.Ekkebus, Y.Kulathu, T.Wauer, F.El Oualid, S.M.Freund, H.Ovaa, D.Komander.

ABSTRACT

Sixteen ovarian tumor (OTU) family deubiquitinases (DUBs) exist in humans, and most members regulate cell-signaling cascades. Several OTU DUBs were reported to be ubiquitin (Ub) chain linkage specific, but comprehensive analyses are missing, and the underlying mechanisms of linkage specificity are unclear. Using Ub chains of all eight linkage types, we reveal that most human OTU enzymes are linkage specific, preferring one, two, or a defined subset of linkage types, including unstudied atypical Ub chains. Biochemical analysis and five crystal structures of OTU DUBs with or without Ub substrates reveal four mechanisms of linkage specificity. Additional Ub-binding domains, the ubiquitinated sequence in the substrate, and defined S1' and S2 Ub-binding sites on the OTU domain enable OTU DUBs to distinguish linkage types. We introduce Ub chain restriction analysis, in which OTU DUBs are used as restriction enzymes to reveal linkage type and the relative abundance of Ub chains on substrates.