1rkk
From Proteopedia
(New page: 200px<br /><applet load="1rkk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rkk" /> '''POLYPHEMUSIN I NMR SOLUTION STRUCTURE'''<br ...) |
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'''POLYPHEMUSIN I NMR SOLUTION STRUCTURE'''<br /> | '''POLYPHEMUSIN I NMR SOLUTION STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The solution structure of polyphemusin I was determined using (1)H-NMR | + | The solution structure of polyphemusin I was determined using (1)H-NMR spectroscopy. Polyphemusin I was found to be an amphipathic, beta-hairpin connected by a type I' beta-turn. The 17 low-energy structures aligned very well over the beta-sheet region while both termini were poorly defined due in part to a hinge-like region centred in the molecule about arginine residues 6 and 16. Conversely, a linear analogue, PM1-S, with all cysteines simultaneously replaced with serine was found to be dynamic in nature, and a lack of medium and long-range NOEs indicated that this molecule displayed no favoured conformation. Circular dichroism (CD) spectroscopy confirmed that in solution, 50% trifluoroethanol (TFE) and in the presence of liposomes, PM1-S remained unstructured. The antimicrobial activity of PM1-S was found to be 4- to 16-fold less than that of polyphemusin I and corresponded with a 4-fold reduction in bacterial membrane depolarization. Both peptides were able to associate with lipid bilayers in a similar fashion; however, PM1-S was completely unable to translocate model membranes while polyphemusin I retained this activity. It was concluded that the disulfide-constrained, beta-sheet structure of polyphemusin I is required for maximum antimicrobial activity. Disruption of this structure results in reduced antimicrobial activity and completely abolishes membrane translocation indicating that the linear PM1-S acts through a different antimicrobial mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 1RKK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1RKK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1RKK OCA]. |
==Reference== | ==Reference== | ||
Structure-activity relationships for the beta-hairpin cationic antimicrobial peptide polyphemusin I., Powers JP, Rozek A, Hancock RE, Biochim Biophys Acta. 2004 May 6;1698(2):239-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15134657 15134657] | Structure-activity relationships for the beta-hairpin cationic antimicrobial peptide polyphemusin I., Powers JP, Rozek A, Hancock RE, Biochim Biophys Acta. 2004 May 6;1698(2):239-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15134657 15134657] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hancock, R | + | [[Category: Hancock, R E.W.]] |
| - | [[Category: Powers, J | + | [[Category: Powers, J P.S.]] |
[[Category: Rozek, A.]] | [[Category: Rozek, A.]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
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[[Category: polyphemusin]] | [[Category: polyphemusin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:51:52 2008'' |
Revision as of 12:51, 21 February 2008
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POLYPHEMUSIN I NMR SOLUTION STRUCTURE
Overview
The solution structure of polyphemusin I was determined using (1)H-NMR spectroscopy. Polyphemusin I was found to be an amphipathic, beta-hairpin connected by a type I' beta-turn. The 17 low-energy structures aligned very well over the beta-sheet region while both termini were poorly defined due in part to a hinge-like region centred in the molecule about arginine residues 6 and 16. Conversely, a linear analogue, PM1-S, with all cysteines simultaneously replaced with serine was found to be dynamic in nature, and a lack of medium and long-range NOEs indicated that this molecule displayed no favoured conformation. Circular dichroism (CD) spectroscopy confirmed that in solution, 50% trifluoroethanol (TFE) and in the presence of liposomes, PM1-S remained unstructured. The antimicrobial activity of PM1-S was found to be 4- to 16-fold less than that of polyphemusin I and corresponded with a 4-fold reduction in bacterial membrane depolarization. Both peptides were able to associate with lipid bilayers in a similar fashion; however, PM1-S was completely unable to translocate model membranes while polyphemusin I retained this activity. It was concluded that the disulfide-constrained, beta-sheet structure of polyphemusin I is required for maximum antimicrobial activity. Disruption of this structure results in reduced antimicrobial activity and completely abolishes membrane translocation indicating that the linear PM1-S acts through a different antimicrobial mechanism.
About this Structure
1RKK is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Structure-activity relationships for the beta-hairpin cationic antimicrobial peptide polyphemusin I., Powers JP, Rozek A, Hancock RE, Biochim Biophys Acta. 2004 May 6;1698(2):239-50. PMID:15134657
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