6c4m
Yersinopine dehydrogenase (YpODH) - NADP+ boundYersinopine dehydrogenase (YpODH) - NADP+ bound
Structural highlights
Publication Abstract from PubMedOpine dehydrogenases (ODH) from the bacterial pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Yersinia pestis 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 the important role of this pathway in metal acquisition and virulence, including in lung and burn wound infections (P. aeruginosa) and in blood and heart infections (S. aureus). Here, we present a kinetic and structural characterization of these three opine dehydrogenases. A steady-state kinetic analysis revealed that the three enzymes differ in 6;-keto acid and NAD(P)H substrate specificity, and nicotianamine-like substrate stereoselectivity. To explore the structural basis for these differences, we solved five ODH X-ray crystal structures, ranging in resolution from 1.9 A to 2.5 A, 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 6;-keto acid and nicotianamine-like substrates and for catalysis. This work reports structural and kinetic analyses of enzymes involved in opine metallophore biosynthesis in three important bacterial pathogens of humans. Staphylopine, pseudopaline and yersinopine dehydrogenases: a structural and kinetic analysis of a new functional class of opine dehydrogenase.,McFarlane JS, Davis CL, Lamb AL J Biol Chem. 2018 Apr 4. pii: RA118.002007. doi: 10.1074/jbc.RA118.002007. PMID:29618515[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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