| Investigation of the substrate specificity of lacticin 481 synthetase by using nonproteinogenic amino acids. | |
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MedLine Citation:
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PMID: 19222036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lantibiotics are peptide antimicrobial compounds that are characterized by the thioether-bridged amino acids lanthionine and methyllanthionine. For lacticin 481, these structures are installed in a two-step post-translational modification process by a bifunctional enzyme, lacticin 481 synthetase (LctM). LctM catalyzes the dehydration of Ser and Thr residues to generate dehydroalanine or dehydrobutyrine, respectively, and the subsequent intramolecular regio- and stereospecific Michael-type addition of cysteines onto the dehydroamino acids. In this study, semisynthetic substrates containing nonproteinogenic amino acids were prepared by expressed protein ligation and [3+2]-cycloaddition of azide and alkyne-functionalized peptides. LctM demonstrated broad substrate specificity toward substrates containing beta-amino acids, D-amino acids, and N-alkyl amino acids (peptoids) in certain regions of its peptide substrate. These findings showcase its promise for use in lantibiotic and peptide-engineering applications, whereby nonproteinogenic amino acids might impart improved stability or modulated biological activities. Furthermore, LctM permitted the incorporation of an alkyne-containing amino acid that can be utilized for the site-selective modification of mature lantibiotics and used in target identification. |
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Authors:
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Matthew R Levengood; Christopher C Kerwood; Champak Chatterjee; Wilfred A van der Donk |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chembiochem : a European journal of chemical biology Volume: 10 ISSN: 1439-7633 ISO Abbreviation: Chembiochem Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-03-30 Completed Date: 2009-06-08 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 100937360 Medline TA: Chembiochem Country: Germany |
Other Details:
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Languages: eng Pagination: 911-9 Citation Subset: IM |
Affiliation:
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Department of Chemistry, University of Illinois at Urbana-Champaign, Howard Hughes Medical Institute, 600 S. Mathews Avenue, Urbana, IL 61801, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Amino Acids / chemistry, metabolism* Anti-Bacterial Agents / metabolism* Bacteriocins / metabolism* Enzymes / metabolism* Molecular Sequence Data Molecular Structure Peptides / chemistry, genetics, metabolism Protein Processing, Post-Translational Sequence Alignment Substrate Specificity |
| Grant Support | |
ID/Acronym/Agency:
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GM58822/GM/NIGMS NIH HHS; R01 GM058822-09/GM/NIGMS NIH HHS; T32 GM008276/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Anti-Bacterial Agents; 0/Bacteriocins; 0/Enzymes; 0/LctM protein, Lactococcus lactis; 0/Peptides; 136959-47-2/lacticin 481 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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