PDBsum entry 5jtj

Hydrolase

PDB id: 5jtj

Contents

Protein chains

356 a.a.

76 a.a.

Metals

_CA

PDB id:

5jtj

Name:

Hydrolase

Title:

Usp7cd-ctp in complex with ubiquitin

Structure:

Ubiquitin carboxyl-terminal hydrolase 7,ubiquitin carboxyl- terminal hydrolase 7. Chain: a. Fragment: unp residues 193-538 linked via ggsgg to residues 1084- 1102. Synonym: deubiquitinating enzyme 7,herpesvirus-associated ubiquitin- specific protease,ubiquitin thioesterase 7,ubiquitin-specific- processing protease 7,deubiquitinating enzyme 7,herpesvirus- associated ubiquitin-specific protease,ubiquitin thioesterase 7,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: usp7, hausp. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ubb. Expression_system_taxid: 562

Resolution:

3.32Å R-factor: 0.192 R-free: 0.209

Authors:

J.M.Murray,L.Rouge

Key ref:

L.Rougé et al. (2016). Molecular Understanding of USP7 Substrate Recognition and C-Terminal Activation. Structure, 24, 1335-1345. PubMed id: 27452404 DOI: 10.1016/j.str.2016.05.020

Date:

09-May-16 Release date: 10-Aug-16

Protein chain

Q93009  (UBP7_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 7 from Homo sapiens

Seq: 1102 a.a.

Struc: 356 a.a.*

Protein chain

P0CG47  (UBB_HUMAN) -  Polyubiquitin-B from Homo sapiens

Seq: 229 a.a.

Struc: 76 a.a.

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: 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.str.2016.05.020

Structure 24:1335-1345 (2016)

PubMed id: 27452404

Molecular Understanding of USP7 Substrate Recognition and C-Terminal Activation.

L.Rougé, T.W.Bainbridge, M.Kwok, R.Tong, P.Di Lello, I.E.Wertz, T.Maurer, J.A.Ernst, J.Murray.

ABSTRACT

The deubiquitinating enzyme USP7 has a pivotal role in regulating the stability of proteins involved in fundamental cellular processes of normal biology and disease. Despite the importance of USP7, the mechanisms underlying substrate recognition and catalytic activation are poorly understood. Here we present structural, biochemical, and biophysical analyses elucidating the molecular mechanism by which the C-terminal 19 amino acids of USP7 (residues 1084-1102) enhance the ubiquitin cleavage activity of the deubiquitinase (DUB) domain. Our data demonstrate that the C-terminal peptide binds the activation cleft in the catalytic domain and stabilizes the catalytically competent conformation of USP7. Additional structures of longer fragments of USP7, as well as solution studies, provide insight into full-length USP7, the role of the UBL domains, and demonstrate that both substrate recognition and deubiquitinase activity are highly regulated by the catalytic and noncatalytic domains of USP7, a feature that could be essential for the proper function of multi-domain DUBs.