9E3V

Backbone Modification in the Fungal Defensin Plectasin: Prototype NZ2114

9E3V の概要

• エントリーDOI: 10.2210/pdb9e3v/pdb
• 関連するPDBエントリー: 3E7U 6K50
• NMR情報: BMRB: 31207
• 分子名称: Fungal defensin plectasin variant NZ2114 (1 entity in total)
• 機能のキーワード: plectasin derivative, defensin, antibiotic, antimicrobial protein
• 由来する生物種: Pseudoplectania nigrella (Ebony cup)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4423.07

構造登録者

Harmon, T.W.,Song, J.,Gulewicz, A.J.,Di, Y.P.,Horne, W.S. (登録日: 2024-10-24, 公開日: 2025-01-08, 最終更新日: 2025-03-19)

主引用文献

Harmon, T.W.,Song, J.,Gulewicz, A.J.,Di, Y.P.,Horne, W.S.
Structural and Functional Mimicry of the Antimicrobial Defensin Plectasin by Analogues with Engineered Backbone Composition.
Chembiochem, 26:e202400951-e202400951, 2025

PubMed Abstract: The threat posed by bacteria resistant to common antibiotics creates an urgent need for novel antimicrobials. Non-ribosomal peptide natural products that bind Lipid II, such as vancomycin, represent a promising source for such agents. The fungal defensin plectasin is one of a family of ribosomally produced miniproteins that also exert antimicrobial activity via Lipid II binding. Made up entirely of canonical amino acids, these molecules are potentially more susceptible to degradation by protease enzymes than non-ribosomal counterparts. Here, we report the development of proteomimetic variants of plectasin through the systematic incorporation of artificial backbone connectivity in the domain. An iterative secondary-structure-based design scheme yields a variant with a tertiary fold indistinguishable from the prototype natural product, potent activity against Gram positive bacteria, and low mammalian cell toxicity. Backbone modification is shown to improve oxidative folding efficiency of the disulfide-rich scaffold as well as resistance to proteolytic hydrolysis. These results broaden the scope of design strategies toward protein mimetics as well as folds and biological functions possible in such agents.

PubMed: 39714882
DOI: 10.1002/cbic.202400951

実験手法

SOLUTION NMR