429 research outputs found
Calorimetric scrutiny of lipid binding by sticholysin II toxin mutants
The mechanisms by which pore-forming toxins are able to insert into lipid
membranes are a subject of the highest interest in the field of lipid–protein
interaction. Eight mutants affecting different regions of sticholysin II, a
member of the pore-forming actinoporin family, have been produced, and
their hemolytic and lipid-binding properties were compared to those of the
wild-type protein. A thermodynamic approach to the mechanism of pore
formation is also presented. Isothermal titration calorimetry experiments
show that pore formation by sticholysin II is an enthalpy-driven process
that occurs with a high affinity constant (1.7×108 M−1). Results suggest that
conformational flexibility at the N-terminus of the protein does not provide
higher affinity for the membrane, although it is necessary for correct pore
formation. Membrane binding is achieved through two separate mechanisms,
that is, recognition of the lipid–water interface by a cluster of aromatic
residues and additional specific interactions that include a phosphocholinebinding
site. Thermodynamic parameters derived from titration experiments
are discussed in terms of a putative model for pore formation
Perfect Powers: Pillai's works and their developments
After a short introduction to Pillai's work on Diophantine questions, we
quote some later developments and we discuss related open problems.Comment: Submitted for publication in Pillai's collected paper
Characterization of the Interactions between Fluoroquinolone Antibiotics and Lipids: a Multitechnique Approach
Probing drug/lipid interactions at the molecular level represents an important challenge in pharmaceutical research and membrane biophysics. Previous studies showed differences in accumulation and intracellular activity between two fluoroquinolones, ciprofloxacin and moxifloxacin, that may actually result from their differential susceptibility to efflux by the ciprofloxacin transporter. In view of the critical role of lipids for the drug cellular uptake and differences observed for the two closely related fluoroquinolones, we investigated the interactions of these two antibiotics with lipids, using an array of complementary techniques. Moxifloxacin induced, to a greater extent than ciprofloxacin, an erosion of the DPPC domains in the DOPC fluid phase (atomic force microscopy) and a shift of the surface pressure-area isotherms of DOPC/DPPC/fluoroquinolone monolayer toward lower area per molecule (Langmuir studies). These effects are related to a lower propensity of moxifloxacin to be released from lipid to aqueous phase (determined by phase transfer studies and conformational analysis) and a marked decrease of all-trans conformation of acyl-lipid chains of DPPC (determined by ATR-FTIR) without increase of lipid disorder and change in the tilt between the normal and the germanium surface (also determined by ATR-FTIR). All together, differences of ciprofloxacin as compared to moxifloxacin in their interactions with lipids could explain differences in their cellular accumulation and susceptibility to efflux transporters
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