Substrate specificity of the Escherichia coli 4-aminobutyrate carrier encoded by gabP: Uptake and counterflow of structurally diverse molecules

Transport of 4-aminobutyrate into Escherichia coli is catalyzed by gab permease (GabP). Although published studies show that GabP is relatively specific, recognizing the common α-amino acids with low affinity, recent work from this laboratory indicates that a number of synthetic compounds are high affinity transport inhibitors (50% inhibition at 5-100 μM). Here we present evidence that many of these structurally heterogeneous compounds not only inhibit transport but also function as alternative GabP substrates (i.e. a set of observations inconsistent with the idea that the core of the GabP transport channel exhibits rigid structural specificity for the native substrate, 4-aminobutyrate).