Structural and Mutational Analyses of Aspergillus fumigatus SidA: A Flavin-Dependent N-hydroxylating Enzyme
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منابع مشابه
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 eluci...
متن کاملAspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor.
Ferrichrome is a hydroxamate-containing siderophore produced by the pathogenic fungus Aspergillus fumigatus under iron-limiting conditions. This siderophore contains N(5)-hydroxylated l-ornithines essential for iron binding. A. fumigatus siderophore A (Af SidA) catalyzes the flavin- and NADPH-dependent hydroxylation of l-ornithine in ferrichrome biosynthesis. Af SidA was recombinantly expressed...
متن کاملContribution to catalysis of ornithine binding residues in ornithine N5-monooxygenase.
The SidA ornithine N5-monooxygenase from Aspergillus fumigatus is a flavin monooxygenase that catalyzes the NADPH-dependent hydroxylation of ornithine. Herein we report a mutagenesis study targeting four residues that contact ornithine in crystal structures of SidA: Lys107, Asn293, Asn323, and Ser469. Mutation of Lys107 to Ala abolishes activity as measured in steady-state oxygen consumption an...
متن کاملMechanistic and structural studies of the N-hydroxylating flavoprotein monooxygenases.
The N-hydroxylating flavoprotein monooxygenases are siderophore biosynthetic enzymes that catalyze the hydroxylation of the sidechain amino-group of ornithine or lysine or the primary amino-group of putrescine. This hydroxylated product is subsequently formylated or acylated and incorporated into the siderophore. Importantly, the modified amino-group is a hydroxamate and serves as an iron chela...
متن کاملMonitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Aspergillus fumigatus siderophore A (SidA) is an FAD-containing monooxygenase that catalyzes the hydroxylation of ornithine in the biosynthesis of hydroxamate siderophores that are essential for virulence (e.g. ferricrocin or N',N",N'''-triacetylfusarinine C). The reaction catalyzed by SidA can be divided into reductive and oxidative half-reactions. In the reductive half-reaction, the oxidized ...
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تاریخ انتشار 2012