| Enhancing the utility of unnatural amino acid synthetases by manipulating broad substrate specificity. | |
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MedLine Citation:
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PMID: 19668869 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Many unnatural amino acid synthetases have been evolved to enable the site-specific in vivo incorporation of many useful functionalities into proteins. While these unnatural amino acid-tRNA synthetase-tRNA(CUA) pairs do not incorporate endogenous amino acids, their substrate specificity has not been assessed for other unnatural amino acids. Here we demonstrate that the unnatural synthetases can be permissive to many unnatural amino acid substrates. The utility of unnatural synthetases can be further expanded by manipulating the synthetase active sites by mutagenesis. Here we have also shown that an l-2-naphthylalanine synthetase can be converted into a permissive l-4-benzoylphenylalanine synthetase with a single mutation without compromising fidelity. Permissive unnatural amino acid synthetases should significantly expand the tool set available for manipulation of proteins. |
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Authors:
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Audrey L Stokes; Shigeki J Miyake-Stoner; Jennifer C Peeler; Duy P Nguyen; Robert P Hammer; Ryan A Mehl |
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Publication Detail:
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Type: Journal Article Date: 2009-05-28 |
Journal Detail:
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Title: Molecular bioSystems Volume: 5 ISSN: 1742-2051 ISO Abbreviation: Mol Biosyst Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-11 Completed Date: 2009-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101251620 Medline TA: Mol Biosyst Country: England |
Other Details:
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Languages: eng Pagination: 1032-8 Citation Subset: IM |
Affiliation:
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Franklin and Marshall College, Department of Chemistry, P.O. Box 3003, Lancaster, PA 17604, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alanine
/
analogs & derivatives,
chemistry,
metabolism Amino Acids / chemistry, metabolism* Amino Acyl-tRNA Synthetases / genetics, metabolism* Computational Biology / methods* Mutagenesis, Site-Directed / methods Phenylalanine / analogs & derivatives, chemistry, metabolism Proteins / metabolism Substrate Specificity |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Proteins; 2566-22-5/benzoylphenylalanine; 56-41-7/Alanine; 63-91-2/Phenylalanine; EC 6.1.1.-/Amino Acyl-tRNA Synthetases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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