| SylC catalyzes ureido-bond formation during biosynthesis of the proteasome inhibitor syringolin A. | |
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MedLine Citation:
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PMID: 19968303 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Syringolins are a class of cyclic tripeptide natural products that are potent and irreversible inhibitors of the eukaryotic proteasome. In addition to being hybrid NRPS/PKS molecules, they also feature an unusual ureido-linkage (red) between two amino acid monomers. Here we report the first in vitro characterization of enzymatic ureido-linkage formation which is catalyzed by an NRPS, SylC. Using (13)C- and (18)O-labeling studies, we show that biosynthesis occurs via N-carboxylation to form an initial N-carboxy-aminoacyl-S-Ppant enzyme intermediate which undergoes intramolecular cyclization followed by condensation with a second amino acid to form the ureido-containing dipeptide product. |
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Authors:
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Heidi J Imker; Christopher T Walsh; William M Wuest |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 131 ISSN: 1520-5126 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-23 Completed Date: 2010-03-02 Revised Date: 2013-04-12 |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 18263-5 Citation Subset: IM |
Affiliation:
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115. USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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chemistry Catalysis Peptides, Cyclic / biosynthesis*, chemical synthesis Proteasome Inhibitors* Urea / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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GM49338/GM/NIGMS NIH HHS; R01 GM049338-17/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Peptides, Cyclic; 0/Proteasome Inhibitors; 0/syringolin A; 57-13-6/Urea |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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