Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases.

SidA from the human pathogen Aspergillus fumigatus catalyzes the generation of N(5)-hydroxyornithine in the biosynthesis of siderophores, a reaction essential for virulence. The crystal structures of SidA in complex with ornithine and lysine reveal the geometry of the interactions among flavin, NADP(+), and the substrate amine group that underlie the hydroxylation reaction. The structural elucidation of the enzyme in complex with arginine provides insight into the role of electrostatics and hydrogen bonding in the mechanism of oxygen activation in this family of enzymes.