Publications

• Staphylopine, pseudopaline, and yersinopine dehydrogenases: A structural and kinetic analysis of a new functional class of opine dehydrogenase.

  McFarlane J.S., Davis C.L., Lamb A.L.

  Opine dehydrogenases (ODHs) from the bacterial pathogens <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, and <i>Yersinia pestis</i> perform the final enzymatic step in the biosynthesis of a new class of opine metallophores, which includes staphylopine, pseudopaline, and yersinopine, r ... >> More

  Opine dehydrogenases (ODHs) from the bacterial pathogens <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, and <i>Yersinia pestis</i> perform the final enzymatic step in the biosynthesis of a new class of opine metallophores, which includes staphylopine, pseudopaline, and yersinopine, respectively. Growing evidence indicates an important role for this pathway in metal acquisition and virulence, including in lung and burn-wound infections (<i>P. aeruginosa</i>) and in blood and heart infections (<i>S. aureus</i>). Here, we present kinetic and structural characterizations of these three opine dehydrogenases. A steady-state kinetic analysis revealed that the three enzymes differ in α-keto acid and NAD(P)H substrate specificity and nicotianamine-like substrate stereoselectivity. The structural basis for these differences was determined from five ODH X-ray crystal structures, ranging in resolution from 1.9 to 2.5 Å, with or without NADP⁺ bound. Variation in hydrogen bonding with NADPH suggested an explanation for the differential recognition of this substrate by these three enzymes. Our analysis further revealed candidate residues in the active sites required for binding of the α-keto acid and nicotianamine-like substrates and for catalysis. This work reports the first structural kinetic analyses of enzymes involved in opine metallophore biosynthesis in three important bacterial pathogens of humans. << Less

  J. Biol. Chem. 293:8009-8019(2018) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Pseudomonas aeruginosa zinc uptake in chelating environment is primarily mediated by the metallophore pseudopaline.

  Lhospice S., Gomez N.O., Ouerdane L., Brutesco C., Ghssein G., Hajjar C., Liratni A., Wang S., Richaud P., Bleves S., Ball G., Borezee-Durant E., Lobinski R., Pignol D., Arnoux P., Voulhoux R.

  Metal uptake is vital for all living organisms. In metal scarce conditions a common bacterial strategy consists in the biosynthesis of metallophores, their export in the extracellular medium and the recovery of a metal-metallophore complex through dedicated membrane transporters. Staphylopine is a ... >> More

  Metal uptake is vital for all living organisms. In metal scarce conditions a common bacterial strategy consists in the biosynthesis of metallophores, their export in the extracellular medium and the recovery of a metal-metallophore complex through dedicated membrane transporters. Staphylopine is a recently described metallophore distantly related to plant nicotianamine that contributes to the broad-spectrum metal uptake capabilities of Staphylococcus aureus. Here we characterize a four-gene operon (PA4837-PA4834) in Pseudomonas aeruginosa involved in the biosynthesis and trafficking of a staphylopine-like metallophore named pseudopaline. Pseudopaline differs from staphylopine with regard to the stereochemistry of its histidine moiety associated with an alpha ketoglutarate moiety instead of pyruvate. In vivo, the pseudopaline operon is regulated by zinc through the Zur repressor. The pseudopaline system is involved in nickel uptake in poor media, and, most importantly, in zinc uptake in metal scarce conditions mimicking a chelating environment, thus reconciling the regulation of the cnt operon by zinc with its function as the main zinc importer under these metal scarce conditions. << Less

  Sci. Rep. 7:17132-17132(2017) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.