AdiC transports arginine and agmatine (the decarboxylation product of arginine) across the membrane of certain enteric bacteria including E. coli, as well as pathognic organisms such as Salmonella. It belongs to the APC (amino acids, polyamines and organic cations) superfamily. Its major role is to maintain the internal pH of the cell in the acidic environment (such as stomach) by functioning as a virtual proton pump-transporting arginine (+ 1 charge) into and agmatine (decarboxylated arginine,+ 2 charge) out of the cell, resulting in export of 1 proton out during each turnover.

We recently solved the crystal structure of AdiC with a Fab fragment at 3.2 Å. The protein is captured in an outward-open, substrate-free conformation. Both structure and functional data have shown that some aromatic residues (Y93, W293 and Y365) are important for the substrate binding and transport, yet we don't have the direct picture of the structure in the presence of either arginine or agmatine. Therefore, our current work is focused on obtaining the conformation with substrate-bound. One approach is to design pair wise cysteines that can crosslink and mimic the conformation with substrate. Comparing the structure of AdiC and several other proteins with similar fold, we are targeting TM2 and TM8 for the cysteine crosslinking now. A second approach, based on our experience with Fab production, is to find another Fab that can stabilize the substrate-bound conformation. Currently we have twelve more monoclonal antibodies that bind AdiC and need to be tested.