1VM5

Solution structure of micelle-bound aurein 1.2, an antimicrobial and anticancer peptide from an Australian frog

1VM5 の概要

• エントリーDOI: 10.2210/pdb1vm5/pdb
• 関連するPDBエントリー: 1O53 1vm2 1vm3 1vm4
• 分子名称: peptide A5 or aurein 1.2 (1 entity in total)
• 機能のキーワード: amphipathic helix, antibacterial peptide, antitumor peptide, micelle, antibiotic
• 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: 1480.77

構造登録者

Wang, G.,Li, X. (登録日: 2004-08-31, 公開日: 2004-12-07, 最終更新日: 2024-11-06)

主引用文献

Wang, G.,Li, Y.,Li, X.
Correlation of Three-dimensional Structures with the Antibacterial Activity of a Group of Peptides Designed Based on a Nontoxic Bacterial Membrane Anchor.
J.Biol.Chem., 280:5803-5811, 2005

PubMed Abstract: To understand the functional differences between a nontoxic membrane anchor corresponding to the N-terminal sequence of the Escherichia coli enzyme IIA(Glc) and a toxic antimicrobial peptide aurein 1.2 of similar sequence, a series of peptides was designed to bridge the gap between them. An alteration of a single residue of the membrane anchor converted it into an antibacterial peptide. Circular dichroism spectra indicate that all peptides are disordered in water but helical in micelles. Structures of the peptides were determined in membrane-mimetic micelles by solution NMR spectroscopy. The quality of the distance-based structures was improved by including backbone angle restraints derived from a set of chemical shifts ((1)H(alpha), (15)N, (13)C(alpha), and (13)C(beta)) from natural abundance two-dimensional heteronuclear correlated spectroscopy. Different from the membrane anchor, antibacterial peptides possess a broader and longer hydrophobic surface, allowing a deeper penetration into the membrane, as supported by intermolecular nuclear Overhauser effect cross-peaks between the peptide and short chain dioctanoyl phosphatidylglycerol. An attempt was made to correlate the NMR structures of these peptides with their antibacterial activity. The activity of this group of peptides does not correlate exactly with helicity, amphipathicity, charge, the number of charges, the size of the hydrophobic surface, or hydrophobic transfer free energy. However, a correlation is established between the peptide activity and membrane perturbation potential, which is defined by interfacial hydrophobic patches and basic residues in the case of cationic peptides. Indeed, (31)P solid state NMR spectroscopy of lipid bilayers showed that the extent of lipid vesicle disruption by these peptides is proportional to their membrane perturbation potential.

PubMed: 15572363
DOI: 10.1074/jbc.M410116200

実験手法

SOLUTION NMR