9E3V
Backbone Modification in the Fungal Defensin Plectasin: Prototype NZ2114
Summary for 9E3V
| Entry DOI | 10.2210/pdb9e3v/pdb |
| Related | 3E7U 6K50 |
| NMR Information | BMRB: 31207 |
| Descriptor | Fungal defensin plectasin variant NZ2114 (1 entity in total) |
| Functional Keywords | plectasin derivative, defensin, antibiotic, antimicrobial protein |
| Biological source | Pseudoplectania nigrella (Ebony cup) |
| Total number of polymer chains | 1 |
| Total formula weight | 4423.07 |
| Authors | Harmon, T.W.,Song, J.,Gulewicz, A.J.,Di, Y.P.,Horne, W.S. (deposition date: 2024-10-24, release date: 2025-01-08, Last modification date: 2025-03-19) |
| Primary citation | 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 Cited by 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: 39714882DOI: 10.1002/cbic.202400951 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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