Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Poster Abstracts

15-POS Board 15 DETERMINING THE RATE-LIMITING STEP IN THE PROTON TRANSPORT OF EMRE Da Teng ; Gregory A Voth 1 ; 1 University of Chicago, Department of Chemistry, Chicago, IL, USA EmrE is a Small Multidrug Resistant (SMR) Transporter family member found in E. coli. It can antiport a variety of polyaromatic cations and protons at a fixed 2:1 stoichiometry, resulting in its resistance to these antiseptic drugs. As a secondary transporter, it undergoes conformation changes that alternate the open side of its central binding site for transportation. However, little is known about how the transportation of two substrates is coupled. Experiments have determined that the conformation alternation happens quickly, at the time scale of milliseconds, regardless of whether the ligands are present. Hence the reason why EmrE does not leak protons rapidly is central to understanding its coupling mechanism. We studied two fundamental proton transport steps in the EmrE function cycle with Multiscale Reactive Molecular Dynamics (MS RMD) and free energy sampling. The resulting free energy profile and rate constant helped identify the controlling factor of the proton leak.

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