PDBsum entry: 1yze

Hydrolase

PDB id: 1yze

Contents

Protein chains

101 a.a. *

99 a.a. *

98 a.a. *

Waters ×90

* Residue conservation analysis

PDB id:

1yze

Name:

Hydrolase

Title:

Crystal structure of the n-terminal domain of usp7/hausp.

Structure:

Ubiquitin carboxyl-terminal hydrolase 7. Chain: a, b, c. Synonym: ubiquitin thiolesterase 7, ubiquitin-specific processing protease 7, deubiquitinating enzyme 7, herpesvirus associated ubiquitin-specific protease. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: usp7, hausp. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.325 R-free: 0.367

Authors:

V.Saridakis,Y.Sheng,F.Sarkari,M.N.Holowaty,K.Shire,T.Nguyen, R.G.Zhang,J.Liao,W.Lee,A.M.Edwards,C.H.Arrowsmith,L.Frappie

Key ref:

V.Saridakis et al. (2005). Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol Cell, 18, 25-36. PubMed id: 15808506 DOI: 10.1016/j.molcel.2005.02.029

Date:

28-Feb-05 Release date: 05-Apr-05

Protein chain

Q93009  (UBP7_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 7

Seq: 1102 a.a.

Struc: 101 a.a.

Protein chain

Q93009  (UBP7_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 7

Seq: 1102 a.a.

Struc: 99 a.a.

Protein chain

Q93009  (UBP7_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 7

Seq: 1102 a.a.

Struc: 98 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.3.1.2.15 - Ubiquitin thiolesterase.
• Reaction: Ubiquitin C-terminal thioester + H₂O = ubiquitin + a thiol

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1016/j.molcel.2005.02.029

Mol Cell 18:25-36 (2005)

PubMed id: 15808506

Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization.

V.Saridakis, Y.Sheng, F.Sarkari, M.N.Holowaty, K.Shire, T.Nguyen, R.G.Zhang, J.Liao, W.Lee, A.M.Edwards, C.H.Arrowsmith, L.Frappier.

ABSTRACT

USP7/HAUSP is a key regulator of p53 and Mdm2 and is targeted by the Epstein-Barr nuclear antigen 1 (EBNA1) protein of Epstein-Barr virus (EBV). We have determined the crystal structure of the p53 binding domain of USP7 alone and bound to an EBNA1 peptide. This domain is an eight-stranded beta sandwich similar to the TRAF-C domains of TNF-receptor associated factors, although the mode of peptide binding differs significantly from previously observed TRAF-peptide interactions in the sequence (DPGEGPS) and the conformation of the bound peptide. NMR chemical shift analyses of USP7 bound by EBNA1 and p53 indicated that p53 binds the same pocket as EBNA1 but makes less extensive contacts with USP7. Functional studies indicated that EBNA1 binding to USP7 can protect cells from apoptotic challenge by lowering p53 levels. The data provide a structural and conceptual framework for understanding how EBNA1 might contribute to the survival of Epstein-Barr virus-infected cells.

Selected figure(s)

Figure 1.
Figure 1. Crystal Structure of the USP7 NTD with EBNA1 Peptide

Figure 3.
Figure 3. The Path and Contacts of the EBNA1 Peptide Bound to USP7

The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 18, 25-36) copyright 2005.

Figures were selected by the author.