7DE8

Crystal Structure of outer membrane protein PorB with G103K mutations from Neisseria meningitidis W135

7DE8 の概要

• エントリーDOI: 10.2210/pdb7de8/pdb
• 関連するPDBエントリー: 3VY8
• 分子名称: Outer membrane protein (1 entity in total)
• 機能のキーワード: porin, outer membrane protein, membrane transport, membrane protein
• 由来する生物種: Neisseria meningitidis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38251.43

構造登録者

Tanabe, M.,Kattner, C. (登録日: 2020-11-02, 公開日: 2021-03-31, 最終更新日: 2023-11-29)

主引用文献

Bartsch, A.,Ives, C.M.,Kattner, C.,Pein, F.,Diehn, M.,Tanabe, M.,Munk, A.,Zachariae, U.,Steinem, C.,Llabres, S.
An antibiotic-resistance conferring mutation in a neisserial porin: Structure, ion flux, and ampicillin binding.
Biochim Biophys Acta Biomembr, 1863:183601-183601, 2021

PubMed Abstract: Gram-negative bacteria cause the majority of highly drug-resistant bacterial infections. To cross the outer membrane of the complex Gram-negative cell envelope, antibiotics permeate through porins, trimeric channel proteins that enable the exchange of small polar molecules. Mutations in porins contribute to the development of drug-resistant phenotypes. In this work, we show that a single point mutation in the porin PorB from Neisseria meningitidis, the causative agent of bacterial meningitis, can strongly affect the binding and permeation of beta-lactam antibiotics. Using X-ray crystallography, high-resolution electrophysiology, atomistic biomolecular simulation, and liposome swelling experiments, we demonstrate differences in drug binding affinity, ion selectivity and drug permeability of PorB. Our work further reveals distinct interactions between the transversal electric field in the porin eyelet and the zwitterionic drugs, which manifest themselves under applied electric fields in electrophysiology and are altered by the mutation. These observations may apply more broadly to drug-porin interactions in other channels. Our results improve the molecular understanding of porin-based drug-resistance in Gram-negative bacteria.

PubMed: 33675718
DOI: 10.1016/j.bbamem.2021.183601

実験手法

X-RAY DIFFRACTION (2.76 Å)