The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is ...the biosynthetically unique 3′‐deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine‐5′‐aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme's mechanism demonstrating that H42 is critical to the enzyme's activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3′‐deoxy pacidamycin moiety with the synthetic anti‐retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds.
Short and sweet: Pac13, a small, monomeric and cofactor‐independent dehydratase, catalyzes the formation of biosynthetically unique 3′‐deoxyuridine, a similar moiety to that present within synthetic retrovirals. Structural and mechanistic insights are reported.
The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is ...the biosynthetically unique 3′‐deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine‐5′‐aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme's mechanism demonstrating that H42 is critical to the enzyme's activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3′‐deoxy pacidamycin moiety with the synthetic anti‐retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds.
Kurz und süß: Pac13, eine kleine, monomere und kofaktorunabhängige Dehydratase, katalysiert die Bildung von biosynthetisch einzigartigem 3′‐Desoxyuridin, einem ähnlichen Strukturmotiv wie in synthetischen Retroviren. Einblicke in Struktur‐ und Mechanismusaspekte werden präsentiert.
A phytochemical investigation of the leaves of Hyperbaena valida resulted in the isolation and characterization of two erythrina-type alkaloids, 1 and 2, which were found to be antagonists at ...nicotinic receptors. Compound 1 was assigned as the new 15-amido-3-demethoxy-2α,3α-methylenedioxyerythroculine and compound 2 as the known 3-demethoxy-2α,3α-methylenedioxyerythroculine. Antagonism of a 100 μM nicotine response was observed for alkaloid 1 (IC50 value of 94 ± 8 μM) and alkaloid 2 (IC50 value of 77 ± 19 μM).
The current study examined changes in prevalence of e-cigarette use and perceptions of the harmfulness of e-cigarette and combustible cigarettes following a campus-wide tobacco ban. Undergraduate ...students completed surveys of tobacco use and perceived product harmfulness. Four samples were collected: in 2013 prior to the ban (n = 792) and in fall 2014 (n = 310), 2015 (n = 208), and 2016 (n = 417). E-cigarette use increased in the years following the ban (p = 0.01) while combustible cigarette use decreased from 2013 to 2016 (p = 0.02). Men were more likely than women to use both products (ps < 0.05). Students' perceptions of the harmfulness of combustible and electronic cigarettes remained stable in the years following the ban (p > 0.05). This study is the first to examine the impact of including e-cigarettes in tobacco free policies. Combustible cigarette use declined, but e-cigarette use increased in the years following the e-cigarette ban. Prospective research is needed to understand the long-term impacts of e-cigarette bans.
Chimpanzees,
Pan troglodytes, produce numerous species-atypical signals when raised in captivity. We examined contextual elements of the use of two of these vocal signals, the ‘raspberry’ and the ...extended grunt. Our results demonstrate that these vocalizations are not elicited by the presence of food, but instead function as attention-getting signals. These findings reveal a heretofore underappreciated category of animal signals: attention-getting sounds produced in novel environmental circumstances. The invention and use of species-atypical signals, considered in relation to group differences in signalling repertoires in apes in their natural habitats, may index a generative capacity in these hominoid species without obvious corollary in other primate species.
PDF
