2i1d: Difference between revisions

Revision as of 18:48, 21 February 2008

DPC micelle-bound NMR structures of Tritrp1

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

2I1D is a Single protein structure of sequence 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

Page seeded by OCA on Thu Feb 21 17:48:00 2008

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OCA

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-[[Image:2i1d.gif|left|200px]]<br /><applet load="2i1d" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2i1d.gif|left|200px]]<br /><applet load="2i1d" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2i1d" />
 '''DPC micelle-bound NMR structures of Tritrp1'''<br />
 ==Overview==
-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.
+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 Structure==
-I1D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2I1D OCA].
+I1D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I1D OCA].
 ==Reference==
 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16997878 16997878]
 [[Category: Single protein]]
-[[Category: Nguyen, L.T.]]
+[[Category: Nguyen, L T.]]
-[[Category: Schibli, D.J.]]
+[[Category: Schibli, D J.]]
 [[Category: NH2]]
 [[Category: turn; antimicrobial peptide; micelle-bound peptide]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 12:05:56 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:48:00 2008''