2fbu
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1vm5|1VM5]], [[2f3a|2F3A]], [[2fbs|2FBS]], [[2fcg|2FCG]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fbu OCA], [http://www.ebi.ac.uk/pdbsum/2fbu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fbu RCSB]</span> | ||
}} | }} | ||
| Line 24: | Line 27: | ||
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
[[Category: Wang, G.]] | [[Category: Wang, G.]] | ||
| - | [[Category: | + | [[Category: aggregation]] |
| + | [[Category: antimicrobial peptide]] | ||
| + | [[Category: aromatic-aromatic interaction]] | ||
| + | [[Category: host defense peptide]] | ||
| + | [[Category: ll-37]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:00:38 2008'' |
Revision as of 00:00, 31 March 2008
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| Related: | 1VM5, 2F3A, 2FBS, 2FCG
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Solution structure of the N-terminal fragment of human LL-37
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
2FBU 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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