2F3A

Solution structure of the LL-37-derived aurein 1.2 analog (LLAA) in membrane-mimetic micelles

2F3A の概要

• エントリーDOI: 10.2210/pdb2f3a/pdb
• 関連するPDBエントリー: 1VM5
• 分子名称: aurein 1.2 analog (1 entity in total)
• 機能のキーワード: antimicrobial peptides; aurein 1.2; ll-37; llaa, antimicrobial protein
• 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: 1722.13

構造登録者

Wang, G.,Li, X.,Peterkofsky, A. (登録日: 2005-11-19, 公開日: 2006-10-17, 最終更新日: 2024-11-20)

主引用文献

Li, X.,Li, Y.,Peterkofsky, A.,Wang, G.
NMR studies of aurein 1.2 analogs
BIOCHIM.BIOPHYS.ACTA, 1758:1203-1214, 2006

PubMed Abstract: Aurein 1.2 is an antimicrobial and anticancer peptide isolated from an Australian frog. To improve our understanding of the mechanism of action, two series of peptides were designed. The first series includes the N-terminal membrane anchor of bacterial glucose-specific enzyme IIA, aurein 1.2, and a newly identified aurein 1.2 analog from human LL-37 (LLAA). The order of antibacterial activity is LLAA>aurein 1.2>>the membrane anchor (inactive). The structure of LLAA in detergent micelles was determined by (1)H NMR spectroscopy, including structural refinement by natural abundance (13)C(alpha), (13)C(beta), and (15)N chemical shifts. The hydrophobic surface area of the 3D structure is related to the retention time of the peptide on a reverse-phase HPLC column. The higher activity of LLAA compared to aurein 1.2 was attributed to additional cationic residues that enhance the membrane perturbation potential. The second peptide series was created by changing the C-terminal phenylalanine (F13) of aurein 1.2 to either phenylglycine or tryptophan. A closer or further location of the aromatic rings to the peptide backbone in the mutants relative to F13 is proposed to cause a drop in activity. Phenylglycine with unique chemical shifts may be a useful NMR probe for structure-activity relationship studies of antimicrobial peptides. To facilitate potential future use for NMR studies, random-coil chemical shifts for phenylglycine (X) were measured using the synthetic peptide GGXGG. Aromatic rings of phenylalanines in all the peptides penetrated 2-5 A below the lipid head group and are essential for membrane targeting as illustrated by intermolecular peptide-lipid NOE patterns.

PubMed: 16716252
DOI: 10.1016/j.bbamem.2006.03.032

実験手法

SOLUTION NMR