Escherichia coli NikR, a repressor with homologs in other bacteria and arch
aea, was identified as a potential new member of the ribbon-helix-helix (be
ta-alpha-alpha) family of transcription factors in profile based sequence s
earches and in structure prediction experiments. Biophysical and biochemica
l characterization of the N-terminal domain of NikR show that it has many f
eatures expected of a beta-alpha-alpha protein including alpha-helical cont
ent, dimeric solution form, concentration dependent thermal stability, and
ability to bind DNA in sequence-specific manner. Mutation of a residue pred
icted to be important for DNA-binding reduces operator affinity but does no
t affect the secondary structure or stability of the protein.