1ti7
CRYSTAL STRUCTURE OF NMRA, A NEGATIVE TRANSCRIPTIONAL REGULATOR, IN COMPLEX WITH NADP AT 1.7A RESOLUTION
Structural highlights
FunctionNMRA_EMENI May be a redox sensor protein. Has much higher affinity for NAD(P) than for NAD(P)H. Has similar affinity for NAD and NADP. Negative transcriptional regulator involved in the post-transcriptional modulation of the GATA-type transcription factor areA, forming part of a system controlling nitrogen metabolite repression (By similarity). Interferes with the interaction between areA and target DNA. Overexpression leads to areA inhibition.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNmrA, 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. The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides.,Lamb HK, Leslie K, Dodds AL, Nutley M, Cooper A, Johnson C, Thompson P, Stammers DK, Hawkins AR J Biol Chem. 2003 Aug 22;278(34):32107-14. Epub 2003 May 22. PMID:12764138[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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