4GCP

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

4GCP の概要

• エントリーDOI: 10.2210/pdb4gcp/pdb
• 関連するPDBエントリー: 4GCQ 4GCS
• 分子名称: 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)
• 機能のキーワード: beta-barrel, protein-drug complex, trimer, non-specific channel, ampicillin binding, outer membrane, membrane protein-antibiotic complex, membrane protein/antibiotic
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cell outer membrane; Multi-pass membrane protein: P02931
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75041.41

構造登録者

Ziervogel, B.K.,Roux, B. (登録日: 2012-07-30, 公開日: 2012-12-19, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.98 Å)