2MOA

Solution NMR structure of peptide ImI1 (peak 2)

2MOA の概要

• エントリーDOI: 10.2210/pdb2moa/pdb
• 関連するPDBエントリー: 1CNL 1E74 1G2G 1IM1 1IMI 2BC7 2C9T 4OS1 4OS2 4OS4 4OS5 4OS6 4OS7
• NMR情報: BMRB: 19932
• 関連するBIRD辞書のPRD_ID: PRD_001232
• 分子名称: Alpha-conotoxin ImI (1 entity in total)
• 機能のキーワード: dithiol amino acid, conotoxin, bicyclic peptide, macrocycle, phage display, toxin
• 由来する生物種: Conus imperialis (Imperial cone)
• 細胞内の位置: Secreted: P50983
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1384.65

構造登録者

Heinis, C.,Chen, S. (登録日: 2014-04-24, 公開日: 2014-09-24, 最終更新日: 2023-11-15)

主引用文献

Chen, S.,Gopalakrishnan, R.,Schaer, T.,Marger, F.,Hovius, R.,Bertrand, D.,Pojer, F.,Heinis, C.
Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides.
Nat Chem, 6:1009-1016, 2014

PubMed Abstract: The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability.

PubMed: 25343607
DOI: 10.1038/nchem.2043

実験手法

SOLUTION NMR