Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine

D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure

Universal Human Rights in the Law of the United States

This Article discusses the relationship in U.S. law between State, Federal, and international authorities on universal human rights. All U.S. State constitutions and the Federal Constitution recognize the inherent or inalienable rights of humanity. Yet despite having long accepted the binding force of universal human rights, U.S. courts and public officials have been hesitant to recognize non-U.S. authorities when identifying, interpreting, or enforcing these rights in practice. The U.S. government and courts view most international treaties and declarations concerning universal human rights as simple restatements of existing constitutional guarantees. U.S. courts and public officials have generally weighed foreign evidence of the requirements of universal human rights according to the legitimacy, importance, and probative value of the source. The undemocratic and illiberal nature of many international institutions makes it unlikely that the U.S. Federal or State legal systems will cede final control over such questions to non-U.S. or multinational authorities at any time in the near future