2a9u

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[[Image:2a9u.gif|left|200px]]
[[Image:2a9u.gif|left|200px]]
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{{Structure
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|PDB= 2a9u |SIZE=350|CAPTION= <scene name='initialview01'>2a9u</scene>, resolution 2.10&Aring;
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The line below this paragraph, containing "STRUCTURE_2a9u", creates the "Structure Box" on the page.
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|SITE=
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|LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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|GENE= USP8, KIAA0055, UBPY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_2a9u| PDB=2a9u | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a9u OCA], [http://www.ebi.ac.uk/pdbsum/2a9u PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a9u RCSB]</span>
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'''Structure of the N-terminal domain of Human Ubiquitin carboxyl-terminal hydrolase 8 (USP8)'''
'''Structure of the N-terminal domain of Human Ubiquitin carboxyl-terminal hydrolase 8 (USP8)'''
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[[Category: Weigelt, J.]]
[[Category: Weigelt, J.]]
[[Category: Xue, S.]]
[[Category: Xue, S.]]
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[[Category: coil-coil]]
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[[Category: Coil-coil]]
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[[Category: hydrolase]]
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[[Category: Hydrolase]]
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[[Category: protease]]
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[[Category: Protease]]
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[[Category: sgc]]
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[[Category: Sgc]]
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[[Category: sh3-binding]]
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[[Category: Sh3-binding]]
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[[Category: structural genomic]]
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[[Category: Structural genomic]]
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[[Category: structural genomics consortium]]
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[[Category: Structural genomics consortium]]
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[[Category: thiol protease]]
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[[Category: Thiol protease]]
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[[Category: ubl conjugation pathway]]
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[[Category: Ubl conjugation pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:47:30 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:49:48 2008''
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Revision as of 15:47, 3 May 2008

Image:2a9u.gif

Template:STRUCTURE 2a9u

Structure of the N-terminal domain of Human Ubiquitin carboxyl-terminal hydrolase 8 (USP8)


Overview

Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated targets such as epidermal growth factor receptors and is involved in clathrin-mediated internalization. In 1182 residues, USP8 contains multiple domains, including coiled-coil, rhodanese, and catalytic domains. We report the first high-resolution crystal structures of these domains and discuss their implications for USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is composed of two five-helix bundles, where the first helices are swapped, and carboxyl-terminal helices are extended in an antiparallel fashion. The structure of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals the canonical rhodanese fold but with a distorted primordial active site. The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. A consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction. The structure of the carboxyl-terminal catalytic domain of USP8 exhibits the conserved tripartite architecture but shows unique traits. Notably, the active site, including the ubiquitin binding pocket, is in a closed conformation, incompatible with substrate binding. The presence of a zinc ribbon subdomain near the ubiquitin binding site further suggests a polyubiquitin-specific binding site and a mechanism for substrate induced conformational changes.

About this Structure

2A9U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8)., Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S, J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. PMID:17035239 Page seeded by OCA on Sat May 3 18:47:30 2008

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