PDBsum entry 2amn

Antimicrobial protein

PDB id: 2amn

Contents

Protein chain

26 a.a.

PDB id:

2amn

Name:

Antimicrobial protein

Title:

Solution structure of fowlicidin-1, a novel cathelicidin antimicrobial peptide from chicken

Structure:

Cathelicidin. Chain: a. Fragment: c-terminal domain, residues 123-148. Engineered: yes

Source:

Synthetic: yes. Other_details: this sequence occurs naturally in chicken

NMR struc:

20 models

Authors:

Y.Xiao,H.Dai,Y.R.Bommineni,O.Prakash,G.Zhang

Key ref:

Y.Xiao et al. (2006). Structure-activity relationships of fowlicidin-1, a cathelicidin antimicrobial peptide in chicken. FEBS J, 273, 2581-2593. PubMed id: 16817888 DOI: 10.1111/j.1742-4658.2006.05261.x

Date:

09-Aug-05 Release date: 18-Jul-06

Protein chain

Q6QLQ5  (CTHL1_CHICK) -  Cathelicidin-1 from Gallus gallus

Seq: 148 a.a.

Struc: 26 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1111/j.1742-4658.2006.05261.x

FEBS J 273:2581-2593 (2006)

PubMed id: 16817888

Structure-activity relationships of fowlicidin-1, a cathelicidin antimicrobial peptide in chicken.

Y.Xiao, H.Dai, Y.R.Bommineni, J.L.Soulages, Y.X.Gong, O.Prakash, G.Zhang.

ABSTRACT

Cationic antimicrobial peptides are naturally occurring antibiotics that are actively being explored as a new class of anti-infective agents. We recently identified three cathelicidin antimicrobial peptides from chicken, which have potent and broad-spectrum antibacterial activities in vitro (Xiao Y, Cai Y, Bommineni YR, Fernando SC, Prakash O, Gilliland SE & Zhang G (2006) J Biol Chem281, 2858-2867). Here we report that fowlicidin-1 mainly adopts an alpha-helical conformation with a slight kink induced by glycine close to the center, in addition to a short flexible unstructured region near the N terminus. To gain further insight into the structural requirements for function, a series of truncation and substitution mutants of fowlicidin-1 were synthesized and tested separately for their antibacterial, cytolytic and lipopolysaccharide (LPS)-binding activities. The short C-terminal helical segment after the kink, consisting of a stretch of eight amino acids (residues 16-23), was shown to be critically involved in all three functions, suggesting that this region may be required for the peptide to interact with LPS and lipid membranes and to permeabilize both prokaryotic and eukaryotic cells. We also identified a second segment, comprising three amino acids (residues 5-7) in the N-terminal flexible region, that participates in LPS binding and cytotoxicity but is less important in bacterial killing. The fowlicidin-1 analog, with deletion of the second N-terminal segment (residues 5-7), was found to retain substantial antibacterial potency with a significant reduction in cytotoxicity. Such a peptide analog may have considerable potential for development as an anti-infective agent.

Selected figure(s)

Figure 2.
Fig. 2. Schematic diagram of sequential and medium distance NOE connectivities and C[ H] chemical shift index for fowlicidin 1. The thickness of the bar reflects the strength of the NOE connectivities.

Figure 3.
Fig. 3. Solution structure of fowlicidin-1. (A) Ribbon stereo-diagram of the restrained minimized average structure of fowlicidin-1. (B) Stereo-diagrams of the backbone trace of the 20 lowest energy structures of fowlicidin-1, with residues 8–16 overlaid. (C) Stereo-diagrams of the backbone trace of the 20 lowest energy structures of fowlicidin-1, with residues 17–25 overlaid. This figure was generated using MOLMOL.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS J (2006, 273, 2581-2593) copyright 2006.

Figures were selected by the author.