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

NmrA is a negative transcriptional regulator involved in the post-translati onal modulation of the GATA-type transcription factor AreA, forming part of a system controlling nitrogen metabolite repression in various fungi. X-ra y structures of two NmrA crystal forms, both to 1.8 Angstrom resolution, sh ow NmrA consists of two domains, including a Rossmann fold. NmrA shows an u nexpected similarity to the short-chain dehydrogenase/reductase (SDR) famil y, 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 nu cleotide binding to NmrA could have a regulatory function. Our results sugg est that other transcription factors possess the SDR fold with functions in cluding RNA binding. The SDR fold appears to have been adapted for other ro les including non-enzymatic control functions such as transcriptional regul ation and is likely to be more widespread than previously recognized.