4GCP

Crystal Structure of E. coli OmpF porin in complex with Ampicillin

Summary for 4GCP

• Entry DOI: 10.2210/pdb4gcp/pdb
• Related: 4GCQ 4GCS
• Descriptor: Outer membrane protein F, (2S,5R,6R)-6-{[(2R)-2-AMINO-2-PHENYLETHANOYL]AMINO}-3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLO[3.2.0]HEPTANE-2-CARBOXYLIC ACID (3 entities in total)
• Functional Keywords: beta-barrel, protein-drug complex, trimer, non-specific channel, ampicillin binding, outer membrane, membrane protein-antibiotic complex, membrane protein/antibiotic
• Biological source: Escherichia coli
• Cellular location: Cell outer membrane; Multi-pass membrane protein: P02931
• Total number of polymer chains: 2
• Total formula weight: 75041.41

Authors

Ziervogel, B.K.,Roux, B. (deposition date: 2012-07-30, release date: 2012-12-19, Last modification date: 2024-02-28)

Primary citation

Ziervogel, B.K.,Roux, B.
The Binding of Antibiotics in OmpF Porin.
Structure, 21:76-87, 2013

PubMed Abstract: 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.

PubMed: 23201272
DOI: 10.1016/j.str.2012.10.014

Experimental method

X-RAY DIFFRACTION (1.98 Å)