Document Detail


Enhancing the utility of unnatural amino acid synthetases by manipulating broad substrate specificity.
MedLine Citation:
PMID:  19668869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article     Date:  2009-05-28
Journal Detail:
Title:  Molecular bioSystems     Volume:  5     ISSN:  1742-2051     ISO Abbreviation:  Mol Biosyst     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101251620     Medline TA:  Mol Biosyst     Country:  England    
Other Details:
Languages:  eng     Pagination:  1032-8     Citation Subset:  IM    
Affiliation:
Franklin and Marshall College, Department of Chemistry, P.O. Box 3003, Lancaster, PA 17604, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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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