PDBsum entry 2foj

Hydrolase

PDB id: 2foj

Contents

Protein chain

137 a.a. *

Ligands

GLY-ALA-ARG-ALA-HIS-SER-SER

Waters ×142

* Residue conservation analysis

PDB id:

2foj

Name:

Hydrolase

Title:

The crystal structure of the n-terminal domain of hausp/usp7 complexed with p53 peptide 364-367

Structure:

Ubiquitin carboxyl-terminal hydrolase 7. Chain: a. Fragment: math domain. Synonym: ubiquitin thiolesterase 7, ubiquitin-specific processing protease 7, deubiquitinating enzyme 7, herpesvirus associated ubiquitin-specific protease. Engineered: yes. P53 peptide. Chain: b.

Source:

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

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.229 R-free: 0.262

Authors:

V.Saridakis,Y.Sheng,F.Sarkari,S.Duan,T.Wu,C.H.Arrowsmith,L.Frappier

Key ref:

Y.Sheng et al. (2006). Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nat Struct Mol Biol, 13, 285-291. PubMed id: 16474402 DOI: 10.1038/nsmb1067

Date:

13-Jan-06 Release date: 14-Feb-06

Protein chain

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

Seq: 1102 a.a.

Struc: 137 a.a.

Enzyme reactions

• Enzyme class: 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: 10.1038/nsmb1067

Nat Struct Mol Biol 13:285-291 (2006)

PubMed id: 16474402

Molecular recognition of p53 and MDM2 by USP7/HAUSP.

Y.Sheng, V.Saridakis, F.Sarkari, S.Duan, T.Wu, C.H.Arrowsmith, L.Frappier.

ABSTRACT

The ubiquitin-specific protease, USP7, has key roles in the p53 pathway whereby it stabilizes both p53 and MDM2. We show that the N-terminal domain of USP7 binds two closely spaced 4-residue sites in both p53 and MDM2, falling between p53 residues 359-367 and MDM2 residues 147-159. Cocrystal structures with USP7 were determined for both p53 peptides and for one MDM2 peptide. These peptides bind the same surface of USP7 as Epstein-Barr nuclear antigen-1, explaining the competitive nature of the interactions. The structures and mutagenesis data indicate a preference for a P/AXXS motif in peptides that bind USP7. Contacts made by serine are identical and crucial for all peptides, and Trp165 in the peptide-binding pocket of USP7 is also crucial. These results help to elucidate the mechanism of substrate recognition by USP7 and the regulation of the p53 pathway.

Selected figure(s)

Figure 1.
Figure 1. Crystal structure of USP7 NTD bound to p53 site 359-PGGS-362. (a) Transparent surface diagrams of p53–USP7. (b) Detailed interactions between USP7 (light gray) and p53 (dark gray). (c) Overlay of p53 (red) and EBNA1 (green) peptides from complex structures. (d) Overlay of p53 (red) and TRANCE-R (yellow) peptides from complex structures, showing conserved interactions with USP7 (purple) and TRAF6 (blue) residues.

Figure 2.
Figure 2. Crystal structure of USP7 NTD bound to p53 site 364-AHSS-367. (a) Transparent surface diagram of USP7 NTD bound by p53 mutant peptide 358-EAGGARAHSS-367 (blue). (b) Detailed interactions between USP7 (light gray) and p53 (dark gray). (c) Overlay of p53 peptides 359-PGGS-362 (red) and 364-AHSS-367 (turquoise) from USP7 complex structures.

Figure 4.
Figure 4. Crystal structure of USP7 NTD bound to MDM2 peptide 4. (a) Transparent surface diagram of MDM2-USP7. (b) Detailed interactions between USP7 (light gray) and MDM2 (dark gray). (c) Overlay of MDM2 (blue) and p53 359-PGGS-362 (red) peptides from USP7 complex structures.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 285-291) copyright 2006.

Figures were selected by the author.

Author's comment

The three figures above relate to the three structures 2foo, 2foj and 2fop as follows:
Figure 1: 2foo USP7-p53 359-362 interaction.
Figure 2: 2foj USP7-p53 364-367 interaction.
Figure 4: 2fop USP7-mdm2 interaction.