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