5w7s

Crystal structure of OxaC in complex with sinefungin and meleagrin

spinqualitylabelsall models 5w7s, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5w7s is a 1 chain structure with sequence from Cbs 219.30. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 9Z1, SFG Related: 5w7p, 5w7r Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Antimicrobial and anti-proliferative meleagrin and oxaline are roquefortine C-derived alkaloids produced by fungi of the genus Penicillium. Tandem O-methylations complete the biosynthesis of oxaline from glandicoline B through meleagrin. Currently, little is known about the role of these methylation patterns in the bioactivity profile of meleagrin and oxaline. To establish the structural and mechanistic basis of methylation in these pathways, crystal structures were determined for two late-stage methyltransferases in the oxaline and meleagrin gene clusters from Penicillium oxalicum and Penicillium chrysogenum. The homologous enzymes OxaG and RoqN were shown to catalyze penultimate hydroxylamine O-methylation to generate meleagrin in vitro. Crystal structures of these enzymes in the presence of methyl donor S-adenosylmethionine revealed an open active site, which lacks an apparent base indicating that catalysis is driven by proximity effects. OxaC was shown to methylate meleagrin to form oxaline in vitro, the terminal pathway product. Crystal structures of OxaC in a pseudo-Michaelis complex containing sinefungin and meleagrin, and in a product complex containing S-adenosyl-homocysteine and oxaline, reveal key active site residues with His313 serving as a base that is activated by Glu369. These data provide structural insights into the enzymatic methylation of these alkaloids that include a rare hydroxylamine oxygen acceptor, and can be used to guide future efforts towards selective derivatization and structural diversification and establishing the role of methylation in bioactivity. Unveiling sequential late-stage methyltransferase reactions in the meleagrin/oxaline biosynthetic pathway.,Newmister SA, Romminger S, Schmidt JJ, Williams RM, Smith JL, Berlinck RGS, Sherman DH Org Biomol Chem. 2018 Aug 24. doi: 10.1039/c8ob01565a. PMID:30141817 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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