2fbu

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 2fbu Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Page seeded by OCA on Mon Nov 12 22:02:43 2007