6RSG

NMR structure of pleurocidin VA in SDS micelles

6RSG の概要

• エントリーDOI: 10.2210/pdb6rsg/pdb
• NMR情報: BMRB: 34405
• 分子名称: Pleurocidin (1 entity in total)
• 機能のキーワード: amp, pleurocidin analogue, winter flounder, sds micelles, sequence optimization, antimicrobial protein
• 由来する生物種: Pseudopleuronectes americanus (Winter flounder)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2662.08

構造登録者

Manzo, G.,Mason, A.J. (登録日: 2019-05-21, 公開日: 2020-12-09, 最終更新日: 2024-06-19)

主引用文献

Manzo, G.,Hind, C.K.,Ferguson, P.M.,Amison, R.T.,Hodgson-Casson, A.C.,Ciazynska, K.A.,Weller, B.J.,Clarke, M.,Lam, C.,Man, R.C.H.,Shaughnessy, B.G.O.,Clifford, M.,Bui, T.T.,Drake, A.F.,Atkinson, R.A.,Lam, J.K.W.,Pitchford, S.C.,Page, C.P.,Phoenix, D.A.,Lorenz, C.D.,Sutton, J.M.,Mason, A.J.
A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy.
Commun Biol, 3:697-697, 2020

PubMed Abstract: Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide-lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15 mg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs.

PubMed: 33247193
DOI: 10.1038/s42003-020-01420-3

実験手法

SOLUTION NMR