1TI7

CRYSTAL STRUCTURE OF NMRA, A NEGATIVE TRANSCRIPTIONAL REGULATOR, IN COMPLEX WITH NADP AT 1.7A RESOLUTION

Replaces:  1PDS

Summary for 1TI7

• Entry DOI: 10.2210/pdb1ti7/pdb
• Descriptor: nitrogen metabolite repression regulator NmrA, POTASSIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: rossmann fold, transcriptional regulation, short chain, dehydrogenase, reductase, nadp binding, nmra, transcription
• Biological source: Emericella nidulans
• Total number of polymer chains: 1
• Total formula weight: 40149.85

Authors

Lamb, H.K.,Leslie, K.,Dodds, A.L.,Nutley, M.,Cooper, A.,Johnson, C.,Thompson, P.,Stammers, D.K.,Hawkins, A.R. (deposition date: 2004-06-02, release date: 2004-06-08, Last modification date: 2023-08-23)

Primary citation

Lamb, H.K.,Leslie, K.,Dodds, A.L.,Nutley, M.,Cooper, A.,Johnson, C.,Thompson, P.,Stammers, D.K.,Hawkins, A.R.
The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides.
J.Biol.Chem., 278:32107-32114, 2003

PubMed Abstract: 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.

PubMed: 12764138
DOI: 10.1074/jbc.M304104200

Experimental method

X-RAY DIFFRACTION (1.7 Å)