Biophysical studies of membrane proteins/peptides. Interaction with ...

apparently the most significant as the efficiency of the quinolones is not directly related
to the water/lipid partition coefficient of the molecules (Vazquez et al., 2001). Indeed,
by either not expressing or expressing structurally changed outer membrane porins,
entrance of quinolones in bacteria is severely impaired (Mascaretti, 2003; Chevalier et
al., 2000).
OmpF is one of the porins involved in the permeation process of quinolones
across the outer membrane of bacteria (Chapman and Georgopapadakou, 1988). It was
the first membrane protein to yield crystals of size and order allowing to be analyzed by
X-ray crystallography (Garavito and Rosenbusch, 1980). This porin forms a homotrimer
in the outer membrane and each monomer presents β-barrel structure in which one of
the loops folds back to the barrel, forming a constriction zone at half the height of the
channel (Figure 1 in section 2 of this Chapter). This loop is expected to contribute
significantly to the control of the permeability of OmpF.
It is not yet know whether OmpF operates as a channel or as an enabler of
quinolones diffusion across the lipid-OmpF interface. Therefore, the knowledge of the
exact type of interaction established by OmpF and quinolones is of great biological
relevance, and could be potentially useful in the development of more effective drugs in
the future. In this chapter, the interaction of OmpF and a second generation quinolone,
ciprofloxacin (CP), was studied. CP is a 6-fluoroquinolone which structure is shown in
Figure IV-1. Recent studies suggested a 1:1 stoichiometry for OmpF-CP interaction
(Neves et al., 2005).
Figure IV-1: Chemical structure of CP.
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