The binding of antibiotics in OmpF porin.
Publication Type:Journal Article
Source:Structure, Volume 21, Issue 1, p.76-87 (2013)
Keywords:Amino Acid Sequence, Ampicillin, Anti-Bacterial Agents, beta-Lactams, Binding Sites, Carbenicillin, Crystallography, X-Ray, Diffusion, Disk Diffusion Antimicrobial Tests, Ertapenem, Escherichia coli, Molecular Dynamics Simulation, Molecular Sequence Data, Porins, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary
<p>The structure of OmpF porin in complex with three common antibiotics (zwitterionic ampicillin, anionic ertapenem, and di-anionic carbenicillin) was determined using X-ray crystallography. The three antibiotics are found to bind within the extracellular and periplasmic pore vestibules, away from the narrow OmpF constriction zone. Using the X-ray structures as a starting point, nonequilibrium molecular dynamics simulations with an applied membrane voltage show that ionic current through the OmpF channel is blocked with bound ampicillin, but not with bound carbenicillin. The susceptibility of Escherichia coli expressing OmpF mutants to ampicillin and carbenicillin was also experimentally characterized using microbiologic assays. These results show that general diffusion by OmpF porins allows for transfer of molecules with varied charged states and give insights into the design of more efficient antibiotics. A better understanding of this mechanism will shed light on nature's way of devising channels able to enhance the transport of molecules through membranes.</p>