Sequence C188-9 order and structural data comparisons allow the family of periplasmic chaperones to be divided into two subfamilies on the basis of the length of the loop connecting β-strand F1 with the donor G1 strand, the FGL and FGS subfamilies having a long and a short loop, respectively [15, 16]. This loop is an important structural element which, in the chaperone-subunit complex, extends the acceptor cleft binding motif of the chaperone G1 donor strand. In the FGS chaperones, the β-strand G1 stabilizes a subunit core by donating only three bulky hydrophobic residues [4, 7].

In the case of FGL chaperones, the G1 binding motif is typically extended by two additional, bulky, alternating hydrophobic residues from a loop region [5, 13]. In the FGL chaperones, the second subunit-binding motif involved in the

DSC mechanism is formed by three bulky hydrophopic residues located in the long N-terminal Selleckchem PARP inhibitor sequence forming the β-strand A1 [5, 13]. The long F1-loop-G1 hairpin of these chaperones is stabilized by the disulfide bond conserved in the whole subfamily [17, 18]. The longer G1 and A1 binding motif of the FGL chaperones correlates with the extended structure of the subunits’ acceptor cleft [13]. The molecular differences in the structure and function of the FGL and the FGS chaperones presented here correlate with the structure of the adhesive organelles which they assemble [13]. not The FGL chaperones assemble organelles composed of only one type of protein subunit and, optionally, the second minor tip subunit [12, 13]. They

are characterized by a thin fimbrial, amorphous or capsule-like morphology. Each subunit of these homopolymeric structures possesses the host-cell receptor binding site or sites; thus, they are polyadhesins. In contrast, the FGS chaperones assemble heteropolymeric, well-structured adhesive pili composed of up to seven different subunits [10, 19]. Pili are monoadhesins, as they possess only one receptor binding subunit located at the tip of the organelle. In addition, the division of chaperones and adhesive organelles into the FGS and FGL families also correlates with the phylogenetic analysis based on the usher ancestry. The FGL organelles belong to the γ3-monophyletic group, while the FGS can be divided into five clades: γ1, γ2, γ4, κ and π [20]. The adhesive organelles of the chaperone-usher type are unique virulence factors specific only to Gram-negative -pathogenic bacteria. The conservation of this mechanism renders it a good potential target for the development of antibacterial agents [21, 22]. The pilicides originally proposed by Svensson et al. in 2001 are a class of low molecular weight agents, derivatives of a dihydrothiazolo ring-fused 2-pyridone scaffold which block formation of pili by affecting the function of chaperone [22].