4EPA

The crystal structure of the ferric yersiniabactin uptake receptor FyuA from Yersinia pestis

4EPA の概要

• エントリーDOI: 10.2210/pdb4epa/pdb
• 関連するPDBエントリー: 4EPF 4EPI
• 分子名称: Pesticin receptor, LAURYL DIMETHYLAMINE-N-OXIDE (2 entities in total)
• 機能のキーワード: tonb dependent transporter, iron import, metal transport
• 由来する生物種: Yersinia pestis
• 細胞内の位置: Cell outer membrane: P46359
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 73108.33

構造登録者

Lukacik, P.,Barnard, T.J.,Buchanan, S.K. (登録日: 2012-04-17, 公開日: 2012-06-20, 最終更新日: 2012-07-04)

主引用文献

Lukacik, P.,Barnard, T.J.,Keller, P.W.,Chaturvedi, K.S.,Seddiki, N.,Fairman, J.W.,Noinaj, N.,Kirby, T.L.,Henderson, J.P.,Steven, A.C.,Hinnebusch, B.J.,Buchanan, S.K.
Structural engineering of a phage lysin that targets Gram-negative pathogens.
Proc.Natl.Acad.Sci.USA, 109:9857-9862, 2012

PubMed Abstract: Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against gram-positive organisms but not against gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a β-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora.

PubMed: 22679291
DOI: 10.1073/pnas.1203472109

実験手法

X-RAY DIFFRACTION (3.2 Å)