Howard Ronald Kaback

My early studies on active transport and bioenergetics in right-side-out (RSO) membrane vesicles from bacteria, primarily Escherichia coli as the paradigm, revolutionized the field of membrane transport, transforming the field from phenomenology to biochemistry. Subsequently, my laboratory pioneered developments in the field: from the initial discovery that RSO vesicles are a well defined system to study transport and other functions to the development of probes for quantifying membrane potentials and pH gradients in microscopic systems to site-directed mutagenesis and Cys-scanning mutagenesis to purifying LacY to near homogeneity in a functional state to obtaining X-ray crystal structures to engineering the permease for all manner of biochemical and biophysical studies. As a result of these developments, a mechanism of lactose/H⁺ symport has been presented. Most of the breakthroughs in the history of this research have been widely selected for inclusion in various textbooks, reference books and teaching materials in many languages for both undergraduate and graduate teaching worldwide. The present goal of the research is to test the detailed molecular mechanism of H⁺-coupled membrane transport by LacY and to examine whether other permeases function with a similar mechanism.