The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides
| Autor: | Kris Leslie, Paul Thompson, Alan Cooper, Margaret Nutley, Alastair R. Hawkins, A. Dodds, David K. Stammers, Christopher L. Johnson, Heather K. Lamb |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Fungal protein Base Sequence Calorimetry Differential Scanning Chemistry Stereochemistry Dehydrogenase Isothermal titration calorimetry Cell Biology Reductase Biochemistry Aspergillus nidulans Fungal Proteins Repressor Proteins Glutamine Transcription (biology) GATA transcription factor NAD+ kinase Oxidation-Reduction Molecular Biology DNA Primers |
| Popis: | NmrA, a transcription repressor involved in the regulation of nitrogen metabolism in Aspergillus nidulans,is a member of the short-chain dehydrogenase reductase superfamily. Isothermal titration calorimetry and differential scanning calorimetry have been used to show NmrA binds NAD+ and NADP+ with similar affinity (average KD 65 microM) but has a greatly reduced affinity for NADH and NADPH (average KD 6.0 mM). The structure of NmrA in a complex with NADP+ reveals how repositioning a His-37 side chain allows the different conformations of NAD+ and NADP+ to be accommodated. Modeling NAD(P)H into NmrA indicated that steric clashes, attenuation of electrostatic interactions, and loss of aromatic ring stacking can explain the differing affinities of NAD(P)+/NAD(P)H. The ability of NmrA to discriminate between the oxidized and reduced forms of the dinucleotides may be linked to a possible role in redox sensing. Isothermal titration calorimetry demonstrated that NmrA and a C-terminal fragment of the GATA transcription factor AreA interacted with a 1:1 stoichiometry and an apparent KD of 0.26 microM. NmrA was unable to bind the nitrogen metabolite repression signaling molecules ammonium or glutamine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|