2f3a
From Proteopedia
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Solution structure of the LL-37-derived aurein 1.2 analog (LLAA) in membrane-mimetic micelles
Overview
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.
About this Structure
2F3A is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
NMR studies of aurein 1.2 analogs., Li X, Li Y, Peterkofsky A, Wang G, Biochim Biophys Acta. 2006 Sep;1758(9):1203-14. Epub 2006 Apr 7. PMID:16716252
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