Mechanism of the chorismate dehydratase MqnA, first enzyme of the futalosine pathway

MqnA, the only chorismate dehydratase known so far, catalyzes the initial step in the biosynthesis of menaquinone via the futalosine pathway. Here we present crystal structures of Streptomyces coelicolor MqnA and its active site variants in complex with chorismate and the product 3-enolpyruvyl-benzoate. Together with activity studies, our data are in line with dehydration proceeding via substrate assisted catalysis, with chorismate acting as catalytic base. Surprisingly, structures of the variant Asn17Asp with co-purified ligand suggest that the enzyme converts to a hydrolase by serendipitous positioning of the carboxyl group. All complex structures presented here exhibit a closed Venus flytrap fold, with the enzyme exploiting the characteristic ligand binding properties of the fold for specific substrate binding and catalysis. The conformational rearrangements that facilitate complete burial of substrate/product, with accompanying topological changes to the enzyme surface, could foster substrate channeling within the biosynthetic pathway.