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

Opine dehydrogenases (ODHs) 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 an important role for 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 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.

Taijin Kyofusho

Anxiety in social situations presumably is found in every culture. However, there may be differences across cultures in the specific ways that this anxiety manifests itself and is subjectively experienced by the sufferer. Taijin kyofusho is a broad term for various socially directed fears. Manifestations range from classic social anxiety disorder symptoms to those found in body dysmporphic disorder, delusional disorder, and olfactory reference syndrome. Though originally thought to be a culturally bound variation of social anxiety found only in East Asian populations, a growing body of evidence also locates it in the West. In contrast to egocentric fears found in social anxiety disorder (e.g., “I will embarrass myself”), prototypical taijin kyofusho symptoms are more other directed (e.g., “I will offend others or make them uncomfortable”). Assessment and treatment options are summarized.