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PDBsum entry 2amn
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Antimicrobial protein
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PDB id
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2amn
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References listed in PDB file
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Key reference
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Title
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Structure-Activity relationships of fowlicidin-1, A cathelicidin antimicrobial peptide in chicken.
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Authors
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Y.Xiao,
H.Dai,
Y.R.Bommineni,
J.L.Soulages,
Y.X.Gong,
O.Prakash,
G.Zhang.
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Ref.
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FEBS J, 2006,
273,
2581-2593.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
FEBS J
(2006,
273,
2581-2593)
copyright 2006.
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