2FOP

The Crystal Structure of the N-terminal domain of HAUSP/USP7 complexed with mdm2 peptide 147-150

Summary for 2FOP

• Entry DOI: 10.2210/pdb2fop/pdb
• Related: 1YY6 1YZE 2FOJ 2FOO
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 7, mdm2 peptide (3 entities in total)
• Functional Keywords: math domain, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q93009
• Total number of polymer chains: 2
• Total formula weight: 18767.76

Authors

Saridakis, V.,Sheng, Y.,Sarkari, F.,Duan, S.,Wu, T.,Arrowsmith, C.H.,Frappier, L. (deposition date: 2006-01-13, release date: 2006-02-14, Last modification date: 2023-08-30)

Primary citation

Sheng, Y.,Saridakis, V.,Sarkari, F.,Duan, S.,Wu, T.,Arrowsmith, C.H.,Frappier, L.
Molecular recognition of p53 and MDM2 by USP7/HAUSP
Nat.Struct.Mol.Biol., 13:285-291, 2006

PubMed 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.

PubMed: 16474402
DOI: 10.1038/nsmb1067

Experimental method

X-RAY DIFFRACTION (2.1 Å)