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  • The EMBO Journal (2001) 20, 6619 - 6626
  • doi:10.1093/emboj/20.23.6619

The structure of the negative transcriptional regulator NmrA reveals a structural superfamily which includes the short-chain dehydrogenase/reductases

D.K. Stammers1,2, J. Ren1, K. Leslie1, C.E. Nichols1,2, H.K. Lamb3, S. Cocklin3, A. Dodds3 and A.R. Hawkins3

  1. Structural Biology Division, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
  2. Oxford Centre for Molecular Sciences, New Chemistry Building, South Parks Road, Oxford OX1 3QT, UK
  3. School of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle NE2 4HH, UK

Correspondence to:

D.K. Stammers, E-mail: daves@strubi.ox.ac.uk

Received 15 August 2001; Accepted 8 October 2001; Revised 8 October 2001

NmrA is a negative transcriptional regulator involved in the post-translational modulation of the GATA-type transcription factor AreA, forming part of a system controlling nitrogen metabolite repression in various fungi. X-ray structures of two NmrA crystal forms, both to 1.8 Å resolution, show NmrA consists of two domains, including a Rossmann fold. NmrA shows an unexpected similarity to the short-chain dehydrogenase/reductase (SDR) family, with the closest relationship to UDP-galactose 4-epimerase. We show that NAD binds to NmrA, a previously unreported nucleotide binding property for this protein. NmrA is unlikely to be an active dehydrogenase, however, as the conserved catalytic tyrosine in SDRs is absent in NmrA, and thus the nucleotide binding to NmrA could have a regulatory function. Our results suggest that other transcription factors possess the SDR fold with functions including RNA binding. The SDR fold appears to have been adapted for other roles including non-enzymatic control functions such as transcriptional regulation and is likely to be more widespread than previously recognized.

  • Keywords:

    • crystal structure,
    • NmrA,
    • short-chain dehydrogenase,
    • reductase,
    • transcriptional regulation