2foo: Difference between revisions

Revision as of 18:23, 21 February 2008

The Crystal Strucure of the N-terminal domain of HAUSP/USP7 complexed with p53 peptide 359-362

OverviewOverview

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.

About this StructureAbout this Structure

2FOO is a Single protein structure of sequence from Homo sapiens. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Full crystallographic information is available from OCA.

ReferenceReference

Molecular recognition of p53 and MDM2 by USP7/HAUSP., Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, Frappier L, Nat Struct Mol Biol. 2006 Mar;13(3):285-91. Epub 2006 Feb 12. PMID:16474402

Page seeded by OCA on Thu Feb 21 17:23:38 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 '''The Crystal Strucure of the N-terminal domain of HAUSP/USP7 complexed with p53 peptide 359-362'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-FOO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FOO OCA].
+FOO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FOO OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Ubiquitin thiolesterase]]
-[[Category: Arrowsmith, C.H.]]
+[[Category: Arrowsmith, C H.]]
 [[Category: Duan, S.]]
 [[Category: Frappier, L.]]
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 [[Category: math domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:08:30 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:38 2008''