6GIK

NMR structure of temporin B L1FK in SDS micelles

6GIK の概要

• エントリーDOI: 10.2210/pdb6gik/pdb
• NMR情報: BMRB: 34273
• 分子名称: temporinB_L1FK (1 entity in total)
• 機能のキーワード: amp, temporin b analogue, structural modification, antimicrobial protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1442.87

構造登録者

Manzo, G.,Mason, J.A. (登録日: 2018-05-12, 公開日: 2018-06-13, 最終更新日: 2024-06-19)

主引用文献

Manzo, G.,Ferguson, P.M.,Gustilo, V.B.,Hind, C.K.,Clifford, M.,Bui, T.T.,Drake, A.F.,Atkinson, R.A.,Sutton, J.M.,Batoni, G.,Lorenz, C.D.,Phoenix, D.A.,Mason, A.J.
Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity.
Sci Rep, 9:1385-1385, 2019

PubMed Abstract: Antimicrobial peptides (AMPs) are a potential source of new molecules to counter the increase in antimicrobial resistant infections but a better understanding of their properties is required to understand their native function and for effective translation as therapeutics. Details of the mechanism of their interaction with the bacterial plasma membrane are desired since damage or penetration of this structure is considered essential for AMPs activity. Relatively modest modifications to AMPs primary sequence can induce substantial changes in potency and/or spectrum of activity but, hitherto, have not been predicted to substantially alter the mechanism of interaction with the bacterial plasma membrane. Here we use a combination of molecular dynamics simulations, circular dichroism, solid-state NMR and patch clamp to investigate the extent to which temporin B and its analogues can be distinguished both in vitro and in silico on the basis of their interactions with model membranes. Enhancing the hydrophobicity of the N-terminus and cationicity of the C-terminus in temporin B improves its membrane activity and potency against both Gram-negative and Gram-positive bacteria. In contrast, enhancing the cationicity of the N-terminus abrogates its ability to trigger channel conductance and renders it ineffective against Gram-positive bacteria while nevertheless enhancing its potency against Escherichia coli. Our findings suggest even closely related AMPs may target the same bacterium with fundamentally differing mechanisms of action.

PubMed: 30718667
DOI: 10.1038/s41598-018-37630-3

実験手法

SOLUTION NMR