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-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 A 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.
Stammers
D K
DK
Structural Biology Division, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, Oxford, UK. daves@strubi.ox.ac.uk
Ren
J
J
Leslie
K
K
Nichols
C E
CE
Lamb
H K
HK
Cocklin
S
S
Dodds
A
A
Hawkins
A R
AR
D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004583:Electrons; D005656:Fungal Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009492:Neurospora crassa / Q000201:enzymology; D011485:Protein Binding; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism; D014534:UDPglucose 4-Epimerase / Q000737:chemistry*
D005656:Fungal Proteins; C441635:NmrA protein, Aspergillus nidulans; D012097:Repressor Proteins; D014157:Transcription Factors; D009243:NAD; D014443:Tyrosine; D014534:UDPglucose 4-Epimerase