Title |
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Specificity of the medaka enteropeptidase serine protease and its usefulness as a biotechnological tool for fusion-protein cleavage
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Creator |
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Accessrights |
open access |
Subject |
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Other
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enteropeptidase
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Other
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cleavage specificity
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Other
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biotechnology tool
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Other
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medaka fish
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NDC
487.71
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Description |
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Abstract
en
We cloned two distinct cDNAs for enteropeptidase (EP) from the intestine of the medaka, Oryzias latipes, which is a small freshwater teleost. The mRNAs code for EP-1 (1036 residues) and EP-2 (1043 residues), both of which have a unique, conserved domain structure of the N-terminal heavy chain and C-terminal catalytic serine protease light chain. When compared with mammalian EP serine proteases, the medaka enzyme exhibited extremely low amidolytic activity for small synthetic peptide substrates. Twelve mutated forms of the medaka EP protease were produced by site-directed mutagenesis. Among them, one mutant protease, E173A, was found to have considerably reduced nonspecific hydrolytic activities both for synthetic and protein substrates without serious reduction of its Asp-Asp-Asp-Asp-Lys (D4K)-cleavage activity. For the cleavage of fusion proteins containing a D4K-cleavage site, the medaka EP proteases were shown to have advantages over their mammalian counterparts. Based on our present data, we propose that the E173A mutant is the most appropriate protease to specifically cleave proteins containing the D4K cleavage sequence.
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Publisher |
en
The National Academy of Sciences of the United States of America
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Date |
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Language |
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Resource Type |
journal article |
Version Type |
AM |
Identifier |
HDL
http://hdl.handle.net/2115/30134
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Relation |
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isVersionOf
DOI
https://doi.org/10.1073/pnas.0610447104
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PMID
17438297
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Journal |
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PISSN
0027-8424
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EISSN
1091-6490
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en
Proceedings of the National Academy of Sciencesof the United States of America
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Volume Number104
Issue Number17
Page Start7021
Page End7026
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File |
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Oaidate |
2023-07-26 |