2i1g
DPC micelle-bound NMR structures of Tritrp5
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OverviewOverview
Tritrpticin is a member of the cathelicidin family of antimicrobial, peptides. Starting from its native sequence (VRRFPWWWPFLRR), eight, synthetic peptide analogs were studied to investigate the roles of, specific residues in its biological and structural properties. This, included amidation of the C-terminus paired with substitutions of its, cationic and Phe residues, as well as the Pro residues that are important, for its two-turn micelle-bound structure. These analogs were determined to, have a significant antimicrobial potency. In contrast, two other peptide, analogs, those with the three Trp residues substituted with either Phe or, Tyr residues are not highly membrane perturbing, as determined by leakage, and flip-flop assays using fluorescence spectroscopy. Nevertheless the Phe, analog has a high activity; this suggests an intracellular mechanism for, antimicrobial activity that may be part of the overall mechanism of action, of native tritrpticin as a complement to membrane perturbation. NMR, experiments of these two Trp-substituted peptides showed the presence of, multiple conformers. The structures of the six remaining Trp-containing, analogs bound to dodecylphosphocholine micelles showed major, well-defined, conformations. These peptides are membrane disruptive and show a wide, range in hemolytic activity. Their micelle-bound structures either retain, the typical turn-turn structure of native tritrpticin or have an extended, alpha-helix. This work demonstrates that closely related antimicrobial, peptides can often have remarkably altered properties with complex, influences on their biological activities.
About this StructureAbout this Structure
2I1G is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structure-function analysis of tritrpticin analogs: potential relationships between antimicrobial activities, model membrane interactions, and their micelle-bound NMR structures., Schibli DJ, Nguyen LT, Kernaghan SD, Rekdal O, Vogel HJ, Biophys J. 2006 Dec 15;91(12):4413-26. Epub 2006 Sep 22. PMID:16997878
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