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1xd3

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{{STRUCTURE_1xd3| PDB=1xd3 | SCENE= }}
{{STRUCTURE_1xd3| PDB=1xd3 | SCENE= }}
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'''Crystal structure of UCHL3-UbVME complex'''
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===Crystal structure of UCHL3-UbVME complex===
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==Overview==
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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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The line below this paragraph, {{ABSTRACT_PUBMED_15531586}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15531586 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15531586}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate., Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R, J Biol Chem. 2005 Jan 14;280(2):1512-20. Epub 2004 Nov 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15531586 15531586]
Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate., Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R, J Biol Chem. 2005 Jan 14;280(2):1512-20. Epub 2004 Nov 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15531586 15531586]
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Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family., Borodovsky A, Ovaa H, Kolli N, Gan-Erdene T, Wilkinson KD, Ploegh HL, Kessler BM, Chem Biol. 2002 Oct;9(10):1149-59. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12401499 12401499]
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A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14., Borodovsky A, Kessler BM, Casagrande R, Overkleeft HS, Wilkinson KD, Ploegh HL, EMBO J. 2001 Sep 17;20(18):5187-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11566882 11566882]
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Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution., Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP, EMBO J. 1997 Jul 1;16(13):3787-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9233788 9233788]
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Structural basis for the specificity of ubiquitin C-terminal hydrolases., Johnston SC, Riddle SM, Cohen RE, Hill CP, EMBO J. 1999 Jul 15;18(14):3877-87. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10406793 10406793]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Active site crossover loop]]
[[Category: Active site crossover loop]]
[[Category: Enzyme-ligand complex]]
[[Category: Enzyme-ligand complex]]
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Revision as of 01:09, 28 July 2008

Template:STRUCTURE 1xd3

Crystal structure of UCHL3-UbVME complex

Template:ABSTRACT PUBMED 15531586

About this Structure

1XD3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate., Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R, J Biol Chem. 2005 Jan 14;280(2):1512-20. Epub 2004 Nov 5. PMID:15531586

Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family., Borodovsky A, Ovaa H, Kolli N, Gan-Erdene T, Wilkinson KD, Ploegh HL, Kessler BM, Chem Biol. 2002 Oct;9(10):1149-59. PMID:12401499

A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14., Borodovsky A, Kessler BM, Casagrande R, Overkleeft HS, Wilkinson KD, Ploegh HL, EMBO J. 2001 Sep 17;20(18):5187-96. PMID:11566882

Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution., Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP, EMBO J. 1997 Jul 1;16(13):3787-96. PMID:9233788

Structural basis for the specificity of ubiquitin C-terminal hydrolases., Johnston SC, Riddle SM, Cohen RE, Hill CP, EMBO J. 1999 Jul 15;18(14):3877-87. PMID:10406793

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