The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with α-lysine at low efficiency. Cell-free extracts contained non-α-lysine substrates of PoxA that modified EF-P by a change in mass consistent with β–lysine, a substrate also predicted by genomic analyses. EF-P was efficiently, functionally, modified with (R)-β-lysine but not (S)-β-lysine or genetically encoded α-amino acids, indicating that PoxA has evolved an activity orthogonal to that of the canonical aminoacyl-tRNA synthetases.
As the first recognized member of the "okadaic acid class" of phosphatase inhibitors, the marine natural product okadaic acid is perhaps the most well-known member of a diverse array of secondary metabolites that have emerged as valuable probes for studying the roles of various cellular protein serine/threonine phosphatases. This review provides a historical perspective on the role that okadaic acid has played in stimulating a broad spectrum of modern scientific research as a result of the natural product's ability to bind to and inhibit important classes of protein serine / threonine phosphatases. The relationships between the structure and biological activities of okadaic acid are briefly reviewed, as well as the structural information regarding the particular cellular receptors protein phosphatases 1 (PP1) and 2A. Laboratory syntheses of okadaic acid and its analogs are thoroughly reviewed. Finally, an interpretation of the critical contacts observed between okadaic acid and PP1 by X-ray crystallography is provided, and specific molecular recognition hypotheses that are testable via the synthesis and assay of non-natural analogs of okadaic acid are suggested.
Considerable theoretical and empirical inquiry has focused on the role codes for violence play in generating crime. A large part of this work has examined the attitudes and codes condoning retaliation and violence as well as the prevalence of these among minorities residing in impoverished neighborhoods. Much about the nature of codes remains unknown, however, and this may in part reflect a narrow interest in beliefs about provocation and uses of violence among the inner-city poor. In this study, we elaborate on a code of violence as part of a system of order and honor as articulated by a network of White, working-class males in a southern U.S. city who participate in bar fights. The findings suggest that the code these men use prohibits predatory violence, puts exclusive limitations on situations that warrant violence, and constrains the level of violence in a fight. We detail the contours of this code (e.g., purpose of fighting, the rules of honorable fighting, and justifications for violating these rules) and discuss the code as both a cause and a consequence of behavior. * We thank Mark Berg and Alex Piquero for their comments on earlier drafts. Direct correspondence to
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