Publications by authors named "J A Plumbridge"

Glucosamine-6-phosphate (GlcN6P) deaminases from Escherichia coli (EcNagBI) and Shewanella denitrificans (SdNagBII) are special examples of what constitute nonhomologous isofunctional enzymes due to their convergence, not only in catalysis, but also in cooperativity and allosteric properties. Additionally, we found that the sigmoidal kinetics of SdNagBII cannot be explained by the existing models of homotropic activation. This study describes the regulatory mechanism of SdNagBII using enzyme kinetics, isothermal titration calorimetry (ITC), and X-ray crystallography.

View Article and Find Full Text PDF

In order to respond to ever-changing environmental cues, bacteria display resilient regulatory mechanisms controlling gene expression. At the post-transcriptional level, this is achieved by a combination of RNA-binding proteins, such as ribonucleases (RNases), and regulatory RNAs, including antisense RNAs (asRNAs). Bound to their complementary mRNA, asRNAs are primary targets for the double-strand-specific endoribonuclease, RNase III.

View Article and Find Full Text PDF

Rationale: Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson's disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear.

Objectives: We tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback.

View Article and Find Full Text PDF

NagC is a transcription factor that represses genes involved in N-acetylglucosamine catabolism in Escherichia coli. Repression by NagC is relieved by interaction with GlcNAc6P, the product of transport of GlcNAc into the cell. The DNA-binding domain of NagC contains a classic helix-turn-helix (HTH) motif, but specific operator recognition requires, in addition, an adjacent linker sequence, which is thought to form an extended wing.

View Article and Find Full Text PDF

Transcription regulatory networks (TRNs) are of central importance for both short-term phenotypic adaptation in response to environmental fluctuations and long-term evolutionary adaptation, with global regulatory genes often being targets of natural selection in laboratory experiments. Here, we combined evolution experiments, whole-genome resequencing, and molecular genetics to investigate the driving forces, genetic constraints, and molecular mechanisms that dictate how bacteria can cope with a drastic perturbation of their TRNs. The crp gene, encoding a major global regulator in Escherichia coli, was deleted in four different genetic backgrounds, all derived from the Long-Term Evolution Experiment (LTEE) but with different TRN architectures.

View Article and Find Full Text PDF