>3D-structure
>5|P06134|ADA regulatory protein (Regulatory protein of adaptative response) [Contains: Methylated-DNA--protein-cysteine methyltransferase (EC 2.1.1.63) (O-6-methylguanine-DNA alkyltransferase)]|Escherichia coli|AraC
The Ada protein is structured in two independent domainslinked by a hinge region that is highly susceptible to proteolytic cleavage.
Cys 321 is the methyl acceptor site required for the removal of the methyl groups from O6-methyl-guanine and O4-methylthymine, two highly mutagenic lesions.
Cys 79 is required for demethylation of phosphometyltriesters in the sugar phosphate backbone.
>7|P26189|ADA regulatory protein (Regulatory protein of adaptative response) [Contains: Methylated-DNA--protein-cysteine methyltransferase (EC 2.1.1.63) (O-6-methylguanine-DNA alkyltransferase)]|Salmonella typhimurium|AraC
Cys-68 and Cys-320, which are potential acceptor sites for the methyl group from the damaged DNA.
>15|P03021|Arabinose operon regulatory protein|Escherichia coli O157:H7|AraC
The crystal structure of the arabinose-binding and dimerization domain of the Escherchia coli gene regulatory protein AraC was determined in the presence and absence of L-arabinose. The 1.5 angstrom structure of the arabinose-bound molecule shows that the protein adopts an unusual fold, binding sugar within a beta barrel and completely burying the arabinose with the amino-terminal arm of the protein. Dimer contacts in the presence of arabinose are mediated by an antiparallel coiled-coil. In the 2.8 angstrom structure of the uncomplexed protein, the amino-terminal arm is disordered, uncovering the sugar-binding pocket and allowing it to serve as an oligomerization interface.
In the absence of arabinose, AraC prefers to loop DNA by binding to two half-sites that are separated by 210 base pairs, and in the presence of arabinose it prefers to bind to adjacently located half-sites. The basis for the change in the DNA binding properties appears to result from an arabinose-induced shift of the N-terminal arms from associating with the DNA-binding domains of AraC to associating with the dimerization domains,light switch mechanism.
This ligand-regulated shift in binding appears to depend on the rigidity of the AraC protein and the DNA. The elimination of the dimerization domains connecting the two DNA binding domains of AraC by a flexible peptide linker provides a protein that mimics AraC in presence of arabinose. Augmenting the flexibility of the DNA between the half-sites of binding results in an arabinose independent AraC binding.
>73|P27246|Multiple antibiotic resistance protein marA|Escherichia coli O157:H7|AraC
The crystal structure of MarA, together with its cognate DNA-binding site consists of two similar subdomains, each containing a helix-turn-helix DNA-binding motif. The two recognition helices of the motifs are inserted into adjacent major groove segments on the same face of DNA but are separated by 27 Amstrongs consequently bending the DNA by approximately 35 degrees. Extensive interactions between the recognition helices and the DNA major groove provide sequence specificity.
The PDB identification is 1BL0.
>75|Q56070|Multiple antibiotic resistance protein marA|Salmonella typhimurium|AraC
The stucture may be similar to Escherichia coli MarA.
>78|P10411|Melibiose operon regulatory protein|Escherichia coli O6|AraC
Like many other members of the AraC family, MelR appears to consist of two domains: a C-terminal DNA-binding domain (made of approximately 100 amino acids) and an N-terminal melibiose-sensing domain of approximately 200 amino acids.
>100|P23217|HTH-type transcriptional regulator qacR|Staphylococcus aureus subsp. aureus Mu50|TetR
The crystal structure showed that QacR is comprised of nine alpha helices. The first three helices of QacR form a three-helix bundle DNA binding domain and contain the helix-turn-helix motif (alpha-helix2 and alpha-helix3). Helices 4 through 9 form the drug binding/dimerization domain. The drug-binding pocket is composed of residues from all helices of the inducer-binding domain except alpha 9, as well as residues from 8'. The portal that constitues the only entry to the ligand-binding site is formed for the divergence of alpha 6, alpha 7, alpha 8 and alpha 8'.
The structure reveal that QacR binds one molecule of inducer per dimer. The crystal structure suggests a possible explanation for the 1:2 drug:QacR stoichiometry. The COOH-terminus of alpha 8, the intervening turn and the NH2-terminus of alpha 9 are apposed to residues in the conformational switch region of alpha 5 and alpha 6 and thus the drug induced coil-to-helix transition forces the movement of alpha 8, turn, alpha 9 into the drug-binding pocket of the neighboring subunit, limiting access to its entrance.
The binding of the drug triggers a coil-to-helix transition such that the COOH-terminus of alpha 5 is elongated by a turn of helix leads to the relocation of alpha 6. The movement of alpha 6 leads to a 9.1 A translation and 36.7º rotation of the DNA-binding domain, relative to the DNA-bound QacR. There is also a pendulum motion of alpha 4 upon drug binding, necessary for retention of interactions between the alpha 6 and alpha 6' helices. In the drug-free subunit of the dimer also occur. The DNA-binding domain of the drug-free subunit undergoes a 3.9 A translation and 18.3º rotation compared to the DNA-bound conformation. Overall, there is a large increase in the center-to-center distance of the recognition helices from 37 A (DNA-bound form) to 48 A (drug-bound form).
The crystal structure of QacR bound to different cationic drugs and dyes  (rhodamine 6R, etidium, dequalinium, berberine, crystal violet and malachite green) shows that QacR exhibits an expansive drug-binding site with four charge-neutralizing residues that line and surround the pocket. There is a large   number of aromatic residues and several polar residues in the pocket than can act in a drug-specific manner as either hydrogen bond donors or acceptors. This structure enables the binding pocket to bind different ligands being a crucial feature in multidrug recognition.
The crystal structure of the QacR-DNA complex showed that two QacR dimers bound the IR1 operator. Each dimer engages DNA major groove in a face almost opposite to the other dimer with an angle between both dimer axes that not reach 180º. The two monomers that form each dimer have been named distal and proximal with respect to the centre of symmetry of IR1.  Every IR1 half-site is bound by two monomers, distal and proximal, from different dimer each one.
>114|P16114|Regulatory protein rns|Escherichia coli|AraC
Rns binds in the major groove of the DNA helix at two locations within a single binding site structure. At binding sites I and II, Rns interacts with the three thymine C5-methyl groups. The pattern of DNase I cleavage and protection when Rns is bound to either site I or site II suggests that it binds along one face of the DNA helix, leaving the other face exposed. For three helical turns the phosphodiester backbone of one face of the DNA helix is fully protected between and flanking the two major groove regions contacted by Rns. Rns binds along one face of the DNA helix forming contacts in two adjacent regions of the major groove. These contacts are different in adjacent major groove regions, and the nucleotides are not conserved between regions. It seems probable that Rns uses both of the predicted helix-turn-helix motifs in its carboxy terminus to contact these different sets of nucleotides. Thus, an asymmetric Rns monomer is probably responsible for all of the contacts at each binding site. The asymmetry of the binding protein is reflected in the sequence asymmetry of each binding site. Because they are asymmetric, these binding sites cannot be identified by simple searches for nucleotide palindromes or repeats.
>115|P27292|Right origin-binding protein|Escherichia coli O157:H7|AraC
Protein data bank ID: 1D5Y.
Two helix-turn-helix(HTH) motifs within Rob's N-terminal domain similar to MarA protein and a unique C-terminal domain that is structurally similar to the E. coli galactose-1-phosphate uridyltransferase enzyme (GalT).
Only the N-terminal HTH reading head closely engages the DNA base pairs in the Rob crystal structure. Rob inserts its N-terminal HTH into the major groove over the A box, making both van der Waals and hydrogen bond interactions with the base pairs of the A box sequence of an unbent DNA duplex.
Unlike MarA, Rob does not utilize its terminal HTH motif to interact specifically with the major groove of the B-box in the co-crystal structure with the micF promoter.
The C-terminal HTH motif lies on the surface of the DNA-helix where it contacts the phosphodiester backbone.
>128|P09164|Tetracycline repressor protein class D|Escherichia coli|TetR
The crystal structure of the class TetR(D) shows that this protein forms stable homodimers. The polypeptide chain of each mononer is folded into 10 alpha-helices with connecting turns and loops: (1) The N-terminal three-helix alpha-helices (1, 2 and 3) form the DNA-binding domain including HTH motif. (2) The core of the protein is formed by helices alpha 5 to 10. It is responsible for dimerization (helices alpha 8 and 10 represent the dimerization motif) and constains a binding tunnel that accommodates tetracycline in presence of a divalent cation. (3) The alpha-helix 4 connect the DNA-binding domain to the rigid TetR core.
When the tetracycline-Mg2+ complex, [MgTc]+, enters two identical binding tunnels within the TetR(D) homodimer, a conformational change takes place. Each inducer binding tunnel has three constituent parts, one hydrophobic and two hydrophilic ones. One of the hydrophilic contact areas binds Tc by hydrogen bonding; the hydrophobic region correctly positions Tc and partially closes the entrance to the binding tunnel; the second hydrophilic region coordinates Mg2+, transduces the induction signal, and completes the process of closing the tunnel entrance. Tc confers binding specificity to TetR while Mg2+ is primarily responsible for induction: After binding to the imidazole Nepsilon of His100, Mg2+ is octahedrally coordinated to the 1,3-ketoenolate group of Tc and to three water molecules. One of these waters forms a hydrogen bond to the hydroxyl group Ogamma of Thr103. The induced 2.5 A movement of Thr103 results in the partial unwinding of helix alpha6, associated with a lateral shift of helices alpha4 and alpha9. They simultaneously close the tunnel entrance and cause the DNA-binding domains to adopt a nonbinding conformation, leading to release of operator DNA and expression of the genes responsible for resistance.
The model, based on the crystal structure, for induction upon tetracycline binding is: In the free dimer, (TetR)2, the two DNA-binding domain are 34 A one of the other (the distance between two consecutives major grooves of B-DNA). With the first movement, the C-terminal turn of the alpha-helix 6 unwinds. This forces a pendulum-like motion of alpha-helix 4, which increases the separation of the attached DNA-binding domain by about 3 A, thus the two DNA-binding motifs of the induced dimer [(TetR)(MgTc)(+)] will be 39 A appart and will be unable to attach to the operators O1 and O2.
>146|Q02458|Urease operon transcriptional activator|Proteus mirabilis|AraC
It is postulated that UreR changes conformation or forms multimeric complexes upon urea binding and is able to bind avidly to specific DNA sequences in the region of the ureD promoter.