5dm0 | pdb_00005dm0

Crystal structure of the plantazolicin methyltransferase BamL in complex with triazolic desmethylPZN analog and SAH

spinqualitylabelsall models 5dm0, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dm0 is a 2 chain structure with sequence from Bacillus velezensis FZB42. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: 5D8, SAH, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A7Z2A9_BACVZ Publication Abstract from PubMed 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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