2fbs: Difference between revisions
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[[Image:2fbs.gif|left|200px]] | [[Image:2fbs.gif|left|200px]] | ||
'''Solution structure of the LL-37 core peptide bound to detergent micelles''' | {{Structure | ||
|PDB= 2fbs |SIZE=350|CAPTION= <scene name='initialview01'>2fbs</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NH2:AMINO GROUP'>NH2</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''Solution structure of the LL-37 core peptide bound to detergent micelles''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2FBS is a [ | 2FBS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FBS OCA]. | ||
==Reference== | ==Reference== | ||
Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region., Li X, Li Y, Han H, Miller DW, Wang G, J Am Chem Soc. 2006 May 3;128(17):5776-85. PMID:[http:// | Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region., Li X, Li Y, Han H, Miller DW, Wang G, J Am Chem Soc. 2006 May 3;128(17):5776-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16637646 16637646] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Li, X.]] | [[Category: Li, X.]] | ||
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[[Category: amphipathic helix; ll-37; host defense peptide; antimicrobial peptide]] | [[Category: amphipathic helix; ll-37; host defense peptide; antimicrobial peptide]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:50:28 2008'' | ||
Revision as of 14:50, 20 March 2008
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| Ligands: | NH2 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Solution structure of the LL-37 core peptide bound to detergent micelles
Overview
To understand the structure and activity relationship of human LL-37, a series of peptide fragments was designed. The N-terminal fragment, LL-37(1-12), was not active, while the C-terminal fragment, LL-37(13-37), killed Escherichia coli, as well as drug-sensitive and drug-resistant cancer cells. A 13-residue core antibacterial and anticancer peptide, corresponding to residues 17-29 of LL-37, was identified based on total correlated spectroscopy by trimming nonessential regions (TOCSY-trim). Because LL-37 acts on bacterial membranes, three-dimensional structures of its fragments were determined in micelles by NMR, including structural refinement by natural abundance 15N and 13C chemical shifts. Aromatic-aromatic interactions in the N-terminal fragment were proposed to be essential for LL-37 aggregation. The LL-37 core peptide adopts a similar structure in the micelles of SDS or dioctanoyl phosphatidylglycerol. This structure is retained in the C-terminal fragment LL-37(13-37) and very likely in intact LL-37 based on peptide-aided signal assignments. The higher antibacterial activity of the LL-37 core peptide than aurein 1.2 was attributed to additional cationic residues. To achieve selective membrane targeting, D-amino acids were incorporated into LL-37(17-32). While the D-peptide showed similar antibacterial activity to the L-diastereomer, it lost toxicity to human cells. Structural analysis revealed hydrophobic defects in the new amphipathic structure of the D-peptide, leading to a much shorter retention time on a reversed-phase HPLC column. It is proposed that hydrophobic defects as a result of incoherent hydrophobic packing provide a structural basis for the improvement in cell selectivity of the LL-37 fragment.
About this Structure
2FBS is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region., Li X, Li Y, Han H, Miller DW, Wang G, J Am Chem Soc. 2006 May 3;128(17):5776-85. PMID:16637646
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