Transcriptional antiterminators and activators containing phosphoenolpyruvate: sugar phosphotransferase system (PTS) regulation domains (PRDs) form a class of bacterial regulatory proteins whose activity is modulated by phosphorylation. These regulators stimulate the expression of genes and operons involved in carbohydrate metabolism. They are characterized by the presence of a duplicated regulatory module of ~100 residues that can be reversibly phosphorylated on histidyl residues by the PTS. PRDs in transcriptional antiterminators and activators are PTS regulatory targets that are (de)phosphorylated in response to the availability of carbon sources [1,2,3,4,5].

The PRD domain comprises one and often two highly conserved histidines. It forms a compact bundle comprising five helices (α1-α5) (see <PDB:1H99>). The core of the PRD module consists of two pairs of antiparallel helices making an angle of ~60°. The first pairs contains the antiparallel helices α1 and α4, while the second pair contains α2 and α5. The third helix (α3) is oriented perpendicularly to α5 at the periphery of the bundle. The helices are connected by loops of varying length [3,4,5].

Some proteins known to contain a PRD domain are listed below:

• Escherichia coli bglG, which mediates the positive regulation of the β- glucoside (bgl) operon by functioning as a transcriptional antiterminator.
• Bacillus subtilis licT, which regulates the expression of operons involved in β-glucoside metabolism.
• Bacillus subtilis licR, the probable licABCH operon regulator.
• Bacillus subtilis levR, which regulates the expression of the levanase operon (levDEFG and sacC). LevR is composed of two domains: a N-terminal section that contains a sigma-54 factor interaction ATP-binding domain and a C-terminal bglG-like domain. LevR could be phosphorylated by levD or levE.
• Bacillus subtilis sacT, which regulates the expression of the sucrose operon (sacPA). SacT is probably phosphorylated by sacP (EII-scr).
• Bacillus subtilis sacY, which regulates the expression of the levansucrase operon (sacBX). SacY is probably phosphorylated by the sacX protein.
• Bacillus stearothermophilus mtlR activator.
• Erwinia chrysanthemi arbG [6], which is involved in the regulation of a β-glucoside operon. ArbG is probably phosphorylated by arbF (EII-bgl).
• Lactobacillus casei lacT [7], involved in the regulation of the lac operon.

As a signature pattern for the PRD domain, we selected a conserved region that includes a conserved histidine that could be the site of phosphorylation. We have also developed a profile, which covers the entire PRD domain.