This superfamily includes HetR, a DNA-binding serine-type protease required for heterocyst differentiation in the nitrogen-fixing cyanobacteria under conditions of nitrogen deprivation. The protein binds to a DNA palindrome upstream of hetP and other genes. The HetR monomer is composed of three distinct domains: the N-terminal domain which is involved in DNA binding, the middle domain designated the "flap", and a slightly smaller C-terminal domain designated the "hood". HetR forms a dimer upon DNA binding. That structure contains four distinct domains: an extended DNA-binding unit containing helix-turn-helix (HTH) motifs comprised of the two N-terminal sequences of the monomer; two histidine-rich flaps protruding on either side of the extended structure; and finally a hood comprised of the two C-terminal sequences. The whole HetR dimer becomes more symmetric in the presence of DNA. Overall, the flap orientations are adjusted to provide a more extended interaction with the twofold symmetric DNA duplex.

This entry describes the flap domain, or the middle domain, which interacts with the phosphate backbone of the DNA. The beta hairpin in the flap domain runs along the minor groove of DNA. In the dimer, the two flap domains protrude away from the central N-terminal-C-terminal core structure. These domains are also in position to contact DNA, perhaps at the exterior phosphates, which could enhance the interaction with DNA throughout the length of HetR.

PFAM:PF03574, INTERPRO:IPR005319,DOI:10.1073/pnas.1305971110,DOI:10.1073/pnas.1106840108