Specific or General - It is All About Solute Interactions with the Pore

Abstract

Recently, Kojima and Nikaido (PNAS, 110: E2629, 2014) examined the idea of potential specificity of porin channels, where -lactam antibiotics’ interaction with the pore-lining residues, demonstrated in vitro, was suggested to facilitate transmembrane transport (PNAS, 99:9789, 2002). The authors came to a conclusion that the binding inside OmpF channel does not significantly affect the penetration of ampicillin and benzylpenicillin.While we emphatically agree with the authors that attractive interactions per se do not constitute the leading imperative in search for an antibiotic with the “magic bullet” potential, it would be surprising if Nature (or pharmaceutical companies, by trial and error) had not explored the benefits of these interactions to facilitate antibiotic translocation. Indeed, the probability of translocation through the OmpF pore for the molecule of ampicillin size that is already at the channel entrance could be estimated as a fraction of one percent (JCP, 116:9952, 2002). This is an impressively small number.The presence of optimal attractive interactions is able to compensate for the entropic cost of confinement (Biochemistry, 52:9246, 2013) and thus increase the translocation probability to 0.5, its maximum value for passive, although interaction-assisted, diffusion. Certainly, not every attractive interaction is optimal or even beneficial for translocation. Too strong or wrongly distributed binding can be detrimental. However, attractive interactions in a particular channel-solute pair are able, at least in principle, to transform a porin, which is “general” for many other solutes, into a “specific” one for the particular pair.