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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/A7Z2A9_BACVZ A7Z2A9_BACVZ] | | [https://www.uniprot.org/uniprot/A7Z2A9_BACVZ A7Z2A9_BACVZ] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Peptide antibiotics represent a class of conformationally constrained natural products of growing pharmaceutical interest. Plantazolicin (PZN) is a linear, polyheterocyclic natural product with highly selective and potent activity against the anthrax-causing bacterium, Bacillus anthracis. The bioactivity of PZN is contingent on dimethylation of its N-terminal Arg residue by an S-adenosylmethionine-dependent methyltransferase. Here, we explore the substrate tolerances of two homologous PZN methyltransferases by carrying out kinetic analyses of the enzymes against a synthetic panel of truncated PZN analogs containing the N-terminal Arg residue. X-ray cocrystal structures of the PZN methyltransferases with each of these heterocycle-containing substrates provide a rationale for understanding the strict substrate specificity of these enzymes. Kinetic studies of structure-guided, site-specific variants allowed for the assignment of residues governing catalysis and substrate scope. Microbiological testing further revealed that upon dimethylation of the N-terminal Arg, a pentaheterocyclized PZN analog retained potent anti-B. anthracis activity, nearly equal to that of full-length PZN. These studies may be useful in the biosynthetic engineering of natural product analogs with different bioactivity profiles, as demonstrated by our identification of a truncated plantazolicin derivative that is active against methicillin-resistant Staphylococcus aureus (MRSA).
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| Insights into methyltransferase specificity and bioactivity of derivatives of the antibiotic plantazolicin.,Hao Y, Blair PM, Sharma A, Mitchell DA, Nair SK ACS Chem Biol. 2015 May 15;10(5):1209-1216. doi: 10.1021/cb501042a. Epub 2015 Feb, 11. PMID:25635336<ref>PMID:25635336</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 5dly" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
