7RN3

hyen D solution structure

7RN3 の概要

• エントリーDOI: 10.2210/pdb7rn3/pdb
• NMR情報: BMRB: 30938
• 分子名称: Cyclotide hyen-D (1 entity in total)
• 機能のキーワード: cyclotides, plant protein
• 由来する生物種: Hybanthus enneaspermus (Spade flower, Viola enneasperma)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3182.78

構造登録者

Du, Q.,Huang, Y.H.,Craik, D.J.,Wang, C.K. (登録日: 2021-07-29, 公開日: 2022-03-02, 最終更新日: 2024-11-13)

主引用文献

Du, Q.,Huang, Y.H.,Wang, C.K.,Kaas, Q.,Craik, D.J.
Mutagenesis of bracelet cyclotide hyen D reveals functionally and structurally critical residues for membrane binding and cytotoxicity.
J.Biol.Chem., 298:101822-101822, 2022

PubMed Abstract: Cyclotides have a wide range of bioactivities relevant for agricultural and pharmaceutical applications. This large family of naturally occurring macrocyclic peptides is divided into three subfamilies, with the bracelet subfamily being the largest and comprising the most potent cyclotides reported to date. However, attempts to harness the natural bioactivities of bracelet cyclotides and engineer-optimized analogs have been hindered by a lack of understanding of the structural and functional role of their constituent residues, which has been challenging because bracelet cyclotides are difficult to produce synthetically. We recently established a facile strategy to make the I11L mutant of cyclotide hyen D that is as active as the parent peptide, enabling the subsequent production of a series of variants. In the current study, we report an alanine mutagenesis structure-activity study of [I11L] hyen D to probe the role of individual residues on peptide folding using analytical chromatography, on molecular function using surface plasmon resonance, and on therapeutic potential using cytotoxicity assays. We found that Glu-6 and Thr-15 are critical for maintaining the structure of bracelet cyclotides and that hydrophobic residues in loops 2 and 3 are essential for membrane binding and cytotoxic activity, findings that are distinct from the structural and functional characteristics determined for other cyclotide subfamilies. In conclusion, this is the first report of a mutagenesis scan conducted on a bracelet cyclotide, offering insights into their function and supporting future efforts to engineer bracelet cyclotides for biotechnological applications.

PubMed: 35283188
DOI: 10.1016/j.jbc.2022.101822

実験手法

SOLUTION NMR