A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

Riboswitches are structured non-coding RNAs often located upstream of essential genes in bacterial messenger RNAs. Such RNAs regulate expression of downstream genes by recognizing a specific cellular effector. Although nearly 50 riboswitch classes are known, only a handful recognize multiple effectors. Here, we report the 2.60-Å resolution co-crystal structure of a class I type I preQ1-sensing riboswitch that reveals two effectors stacked atop one another in a single binding pocket. These effectors bind with positive cooperativity in vitro and both molecules are necessary for gene regulation in bacterial cells. Stacked effector recognition appears to be a hallmark of the largest subgroup of preQ1 riboswitches, including those from pathogens such as Neisseria gonorrhoeae. We postulate that binding to stacked effectors arose in the RNA World to closely position two substrates for RNA-mediated catalysis. These findings expand known effector recognition capabilities of riboswitches and have implications for antimicrobial development.

Low symmetry Pincer Ligands designed for applications in coordination chemistry and catalysis

Pincer ligands are monoanionic, tridentate binding molecules that have been used in coordination chemistry as efficient homogeneous and heterogeneous catalysts (i.e. as transition metal complexes). The focus of this work lies in the synthesis, characterization and coordination chemistry of a series of novel asymmetric potentially monoanionic NN'N", NN'C and NN'P type pincer ligands with amide functionality derived from the skeleton of 2-(2'-anilinyl)-4,4-dimethyl-2-oxazoline. Modular approach to this synthesis has been developed through an alkyl halide intermediate, in addition to the substrate-dependent alternative pincer syntheses, which are also described. The coordination chemistries of Pd and Ni, as well as the potential application of these pincer complexes in metal mediated catalysis of aldehyde allylation reactions will be explored. Moreover, a number of Pd(II) pincer complexes have been successfully synthesized and structurally characterized and these results are likewise described.

Low symmetry Pincer Ligands designed for applications in coordination chemistry and catalysis

Pincer ligands are monoanionic, tridentate binding molecules that have been used in coordination chemistry as efficient homogeneous and heterogeneous catalysts (i.e. as transition metal complexes). The focus of this work lies in the synthesis, characterization and coordination chemistry of a series of novel asymmetric potentially monoanionic NN'N", NN'C and NN'P type pincer ligands with amide functionality derived from the skeleton of 2-(2'-anilinyl)-4,4-dimethyl-2-oxazoline. Modular approach to this synthesis has been developed through an alkyl halide intermediate, in addition to the substrate-dependent alternative pincer syntheses, which are also described. The coordination chemistries of Pd and Ni, as well as the potential application of these pincer complexes in metal mediated catalysis of aldehyde allylation reactions will be explored. Moreover, a number of Pd(II) pincer complexes have been successfully synthesized and structurally characterized and these results are likewise described.

The Profound Influence of Lipid Composition on the Catalysis of the Drug Target NADH Type II Oxidoreductase

Lipids play a pivotal role in cellular respiration, providing the natural environment in which an oxidoreductase interacts with the quinone pool. To date, it is generally accepted that negatively charged lipids play a major role in the activity of quinone oxidoreductases. By changing lipid compositions when assaying a type II NADH:quinone oxidoreductase, we demonstrate that phosphatidylethanolamine has an essential role in substrate binding and catalysis. We also reveal the importance of acyl chain composition, specifically c14:0, on membrane-bound quinone-mediated catalysis. This demonstrates that oxidoreductase lipid specificity is more diverse than originally thought and that the lipid environment plays an important role in the physiological catalysis of membrane-bound oxidoreductases.