Source:http://linkedlifedata.com/resource/pubmed/id/15531586
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2005-1-11
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| pubmed:databankReference | |
| pubmed:abstractText |
Ubiquitin C-terminal hydrolases (UCHs) comprise a family of small ubiquitin-specific proteases of uncertain function. Although no cellular substrates have been identified for UCHs, their highly tissue-specific expression patterns and the association of UCH-L1 mutations with human disease strongly suggest a critical role. The structure of the yeast UCH Yuh1-ubiquitin aldehyde complex identified an active site crossover loop predicted to limit the size of suitable substrates. We report the 1.45 A resolution crystal structure of human UCH-L3 in complex with the inhibitor ubiquitin vinylmethylester, an inhibitor that forms a covalent adduct with the active site cysteine of ubiquitin-specific proteases. This structure confirms the predicted mechanism of the inhibitor and allows the direct comparison of a UCH family enzyme in the free and ligand-bound state. We also show the efficient hydrolysis by human UCH-L3 of a 13-residue peptide in isopeptide linkage with ubiquitin, consistent with considerable flexibility in UCH substrate size. We propose a model for the catalytic cycle of UCH family members which accounts for the hydrolysis of larger ubiquitin conjugates.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/UCHL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin Thiolesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
14
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| pubmed:volume |
280
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1512-20
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15531586-Amino Acid Sequence,
pubmed-meshheading:15531586-Binding Sites,
pubmed-meshheading:15531586-Crystallization,
pubmed-meshheading:15531586-Crystallography, X-Ray,
pubmed-meshheading:15531586-Cysteine,
pubmed-meshheading:15531586-Humans,
pubmed-meshheading:15531586-Hydrolysis,
pubmed-meshheading:15531586-Models, Biological,
pubmed-meshheading:15531586-Models, Molecular,
pubmed-meshheading:15531586-Molecular Sequence Data,
pubmed-meshheading:15531586-Protein Binding,
pubmed-meshheading:15531586-Protein Conformation,
pubmed-meshheading:15531586-Rotation,
pubmed-meshheading:15531586-Sequence Alignment,
pubmed-meshheading:15531586-Substrate Specificity,
pubmed-meshheading:15531586-Ubiquitin,
pubmed-meshheading:15531586-Ubiquitin Thiolesterase,
pubmed-meshheading:15531586-Ubiquitins
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| pubmed:year |
2005
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| pubmed:articleTitle |
Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate.
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| pubmed:affiliation |
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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