The gntR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 60-70 residues present in transcriptional regulators of the gntR family. This family of bacterial regulators is named after Bacillus subtilis gntR, a repressor of the gluconate operon [1,2]. Six subfamilies have been described for the gntR family: fadR, hutC, plmA, mocR, ytrA, and araR, which regulate various biological processes and important bacterial metabolic pathways. The DNA-binding gntR-type HTH domain occurs usually in the N-terminal part. The C-terminal part can contain a subfamily-specific effector-binding domain and/or an oligomerization domain. The fadR-like regulators, representing the largest subfamily, are involved in the regulation of oxidized substrates related to metabolic pathways or metabolism of amino acids. HutC-like proteins are involved in conjugative plasmid transfer in several Streptomyces species. PlmA is a cyanobacterial regulator of plasmid maintenance. The mocR subfamily encompasses proteins homologous to class I aminotransferase proteins, which bind pyridoxal phosphate as a cofactor. Most of the ytrA-like proteins take part in operons involved in ATP-binding cassette (ABC) transport systems. AraR is an autoregulatory protein with a C-terminal domain that binds a carbohydrate effector, similar to that present in regulators of the lacI/galR family (see <PDOC00366>) [3,4].

The crystal structures of fadR show that the N-terminal, DNA binding domain contains a small β-sheet (B) core and three α-helices (H) with a topology H1-B1-H2-H3-B2-B3 (see <PDB:1H9T>). Helices 2 and 3, connected via a tight turn, comprise the helix-turn-helix motif. The anti-parallel β-strands 2 and 3 together with B1 form a small β-sheet, which is called the wing. Helix 3 is termed the recognition helix as in most wHTHs it binds the DNA major groove. Here, only the N-terminal tip of the recognition helix makes specific DNA-contacts and the wing makes unusual sequence-specific contacts to the minor groove. Like other HTH proteins, most gntR-type regulators bind as homodimers to 2-fold symmetric DNA sequences in which each monomer recognizes half of the site [5,6].

Some proteins known to contain a gntR-type HTH domain:

• Bacillus subtilis gntR, a repressor of the gnt operon, which is responsible for gluconate metabolism. In the absence of gluconate, gntR binds to the promoter of the operon. The expression of the operon is induced in the presence of gluconate.
• Escherichia coli fadR, a transcriptional regulator of fatty acid metabolism. In the absence of the acyl-CoA effector, fadR binds specific operator sites, represses the expression of genes involved in fatty acid degradation and import, and activates biosynthetic genes. Binding of acyl-CoA gives conformational changes abolishing DNA binding, which derepresses the catabolic genes and deactivates the anabolic genes.
• Escherichia coli phdR, a transcriptional repressor of the pyruvate dehydrogenase complex.
• Klebsiella aerogenes and Pseudomonas putida hutC, a transcriptional repressor of the histidine utilization (hut) operon.
• Streptomyces lividans korA, a regulator that controls plasmid transfer.
• Rhizobium meliloti mocR, a probable regulator of rhizopine catabolism.
• Bacillus subtilis ytrA, a repressor of the acetoine utilization gene cluster.
• Anabaena sp. strain PCC 7120 plmA, a regulator involved in plasmid maintenance [4].
• Bacillus subtilis araR, a transcriptional repressor of the arabinose operon.

The profile we developed covers the entire gntR-type HTH domain, from the well-conserved part of helix 1 to the end of the wing.