The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides.
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 s...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2003
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| _version_ | 1797080179961495552 |
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| author | Lamb, H Leslie, K Dodds, A Nutley, M Cooper, A Johnson, C Thompson, P Stammers, D Hawkins, A |
| author_facet | Lamb, H Leslie, K Dodds, A Nutley, M Cooper, A Johnson, C Thompson, P Stammers, D Hawkins, A |
| author_sort | Lamb, H |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:56:28Z |
| format | Journal article |
| id | oxford-uuid:883dcf17-13a6-41a3-91d3-833df6971a11 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:56:28Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:883dcf17-13a6-41a3-91d3-833df6971a112022-03-26T22:15:55ZThe negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:883dcf17-13a6-41a3-91d3-833df6971a11EnglishSymplectic Elements at Oxford2003Lamb, HLeslie, KDodds, ANutley, MCooper, AJohnson, CThompson, PStammers, DHawkins, ANmrA, 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. |
| spellingShingle | Lamb, H Leslie, K Dodds, A Nutley, M Cooper, A Johnson, C Thompson, P Stammers, D Hawkins, A The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. |
| title | The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. |
| title_full | The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. |
| title_fullStr | The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. |
| title_full_unstemmed | The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. |
| title_short | The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. |
| title_sort | negative transcriptional regulator nmra discriminates between oxidized and reduced dinucleotides |
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