7ron

Crystal structure of the Friedel-Crafts alkylating enzyme CylK from Cylindospermum licheniforme

spinqualitylabelsall models 7ron, resolution 1.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ron is a 1 chain structure with sequence from Cylindrospermum licheniforme UTEX B 2014. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.68Å Ligands: CA, CL, EDO, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1Y0K711_9NOST Publication Abstract from PubMed The cyanobacterial enzyme CylK assembles the cylindrocyclophane natural products by performing two unusual alkylation reactions, forming new carbon-carbon bonds between aromatic rings and secondary alkyl halide substrates. This transformation is unprecedented in biology, and the structure and mechanism of CylK are unknown. Here, we report X-ray crystal structures of CylK, revealing a distinctive fusion of a Ca(2+)-binding domain and a beta-propeller fold. We use a mutagenic screening approach to locate CylK's active site at its domain interface, identifying two residues, Arg105 and Tyr473, that are required for catalysis. Anomalous diffraction datasets collected with bound bromide ions, a product analog, suggest that these residues interact with the alkyl halide electrophile. Additional mutagenesis and molecular dynamics simulations implicate Asp440 in activating the nucleophilic aromatic ring. Bioinformatic analysis of CylK homologs from other cyanobacteria establishes that they conserve these key catalytic amino acids, but they are likely associated with divergent reactivity and altered secondary metabolism. By gaining a molecular understanding of this unusual biosynthetic transformation, this work fills a gap in our understanding of how alkyl halides are activated and used by enzymes as biosynthetic intermediates, informing enzyme engineering, catalyst design, and natural product discovery. Structural basis for an unprecedented enzymatic alkylation in cylindrocyclophane biosynthesis.,Braffman NR, Ruskoski TB, Davis KM, Glasser NR, Johnson C, Okafor CD, Boal AK, Balskus EP Elife. 2022 Feb 25;11. pii: 75761. doi: 10.7554/eLife.75761. PMID:35212625 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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