Structural basis for an unprecedented enzymatic alkylation in cylindrocyclophane biosynthesis.

ABSTRACT: 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 Ca²⁺-binding domain and a β-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. Additio

SUBMITTER: Braffman NR 

PROVIDER: S-EPMC8916777 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature