Amine oxidation by D-arginine dehydrogenase in Pseudomonas aeruginosa

作者：Ouedraogo Daniel; Ball Jacob; Iyer Archana; Reis Renata A G; Vodovoz Maria; Gadda Giovanni^*

来源：Archives of Biochemistry and Biophysics, 2017, 632: 192-201.

DOI：10.1016/j.abb.2017.06.013

• D-arginine dehydrogenase
• D-amino acid
• Flavoprotein
• FAD
• Oxidation
• Sticky substrate
• Loop dynamics
• Racemization
• D-amino acid oxidase
• Molecular dynamics
• Active site gate

D-Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) is a flavin-dependent oxidoreductase, which is part of a novel two-enzyme racemization system that functions to convert D-arginine to L-arginine. PaDADH contains a noncovalently linked FAD that shows the highest activity with D-arginine. The enzyme exhibits broad substrate specificity towards D-amino acids, particularly with cationic and hydrophobic n-amino acids. Biochemical studies have established the structure and the mechanistic properties of the enzyme. The enzyme is a true dehydrogenase because it displays no reactivity towards molecular oxygen. As established through solvent and multiple kinetic isotope studies, PaDADH catalyzes an asynchronous CH and NH bond cleavage via a hydride transfer mechanism. Steady-state kinetic studies with D-arginine and D-histidine are consistent with the enzyme following a ping-pong bi-bi mechanism. As shown by a combination of crystallography, kinetic and computational data, the shape and flexibility of loop L1 in the active site of PaDADH are important for substrate capture and broad substrate specificity.

• 出版日期2017-10-15