| Substrate filtering by the active site crossover loop in UCHL3 revealed by sortagging and gain-of-function mutations. | |
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MedLine Citation:
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PMID: 19047059 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Determining how deubiquitinating enzymes discriminate between ubiquitin-conjugated substrates is critical to understand their function. Through application of a novel protein cleavage and tagging technique, sortagging, we show that human UCHL3 and the Plasmodium falciparum homologue, members of the ubiquitin C-terminal hydrolase family, use a unique active site crossover loop to restrict access of bulky ubiquitin adducts to the active site. Although it provides connectivity for critical active site residues in UCHL3, physical integrity of the crossover loop is dispensable for catalysis. By enlarging the active site crossover loop, we have constructed gain-of-function mutants that can accept substrates that the parent enzyme cannot, including ubiquitin chains of various linkages. |
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Authors:
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Maximilian W Popp; Katerina Artavanis-Tsakonas; Hidde L Ploegh |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-12-01 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-02 Completed Date: 2009-04-06 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 3593-602 Citation Subset: IM |
Affiliation:
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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Catalysis Catalytic Domain / physiology Cysteine Endopeptidases / chemistry*, genetics, metabolism Humans Mutation Plasmodium falciparum / enzymology*, genetics, metabolism Protein Structure, Secondary / physiology Protozoan Proteins / chemistry*, metabolism Substrate Specificity / physiology Ubiquitin / chemistry*, genetics, metabolism Ubiquitination / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Protozoan Proteins; 0/Ubiquitin; EC 3.1.2.15/UCHL3 protein, human; EC 3.4.22.-/Cysteine Endopeptidases |
| Comments/Corrections | |
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