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Antibiotic PDB id
1vm5
Jmol
Contents
Protein chain
14 a.a.
PDB id:
1vm5
Name: Antibiotic
Title: Solution structure of micelle-bound aurein 1.2, an antimicrobial and anticancer peptide from an australian frog
Structure: Peptide a5 or aurein 1.2. Chain: a. Engineered: yes
Source: Synthetic: yes. Other_details: the peptide was synthesized using the solid- phase method and purified by hplc.
NMR struc: 5 models
Authors: G.Wang,X.Li
Key ref:
G.Wang et al. (2005). Correlation of three-dimensional structures with the antibacterial activity of a group of peptides designed based on a nontoxic bacterial membrane anchor. J Biol Chem, 280, 5803-5811. PubMed id: 15572363 DOI: 10.1074/jbc.M410116200
Date:
31-Aug-04     Release date:   07-Dec-04    
PROCHECK
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 Headers
 References

 

 
DOI no: 10.1074/jbc.M410116200 J Biol Chem 280:5803-5811 (2005)
PubMed id: 15572363  
 
 
Correlation of three-dimensional structures with the antibacterial activity of a group of peptides designed based on a nontoxic bacterial membrane anchor.
G.Wang, Y.Li, X.Li.
 
  ABSTRACT  
 
To understand the functional differences between a nontoxic membrane anchor corresponding to the N-terminal sequence of the Escherichia coli enzyme IIA(Glc) and a toxic antimicrobial peptide aurein 1.2 of similar sequence, a series of peptides was designed to bridge the gap between them. An alteration of a single residue of the membrane anchor converted it into an antibacterial peptide. Circular dichroism spectra indicate that all peptides are disordered in water but helical in micelles. Structures of the peptides were determined in membrane-mimetic micelles by solution NMR spectroscopy. The quality of the distance-based structures was improved by including backbone angle restraints derived from a set of chemical shifts ((1)H(alpha), (15)N, (13)C(alpha), and (13)C(beta)) from natural abundance two-dimensional heteronuclear correlated spectroscopy. Different from the membrane anchor, antibacterial peptides possess a broader and longer hydrophobic surface, allowing a deeper penetration into the membrane, as supported by intermolecular nuclear Overhauser effect cross-peaks between the peptide and short chain dioctanoyl phosphatidylglycerol. An attempt was made to correlate the NMR structures of these peptides with their antibacterial activity. The activity of this group of peptides does not correlate exactly with helicity, amphipathicity, charge, the number of charges, the size of the hydrophobic surface, or hydrophobic transfer free energy. However, a correlation is established between the peptide activity and membrane perturbation potential, which is defined by interfacial hydrophobic patches and basic residues in the case of cationic peptides. Indeed, (31)P solid state NMR spectroscopy of lipid bilayers showed that the extent of lipid vesicle disruption by these peptides is proportional to their membrane perturbation potential.
 
  Selected figure(s)  
 
Figure 8.
FIG. 8. Space-filling models of the antibacterial peptides (viewed from the N terminus of the helix). Green, hydrophobic residues; yellow, cationic residues; mixed colors of red (oxygen), blue (nitrogen), gray (carbon), and white (hydrogen), hydrophilic residues. The structure most resembling the average is shown. The figure was generated using RASMOL (www.umass.edu/microbio/rasmol). 		Figure 9.
FIG. 9. Potential surfaces of peptide A2 (A), peptide A3 (B), peptide A4 (C), and peptide A5 (D). Hydrophobic grooves bordered by positive charges, as shown in D, have a high membrane-perturbation potential. Such a potential (D) is reduced in peptides A2, A3, and A4 as a result of the presence of an acidic residue in the vicinity of the positive charge (C), the lack of a hydrophobic groove (A), or the absence of the positive charge completely (B). Blue, basic residues; red, acidic residues; and white, hydrophobic and neutral residues. The figure was made using MOLMOL (47).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 5803-5811) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18957441 G.Wang, X.Li, and Z.Wang (2009).
APD2: the updated antimicrobial peptide database and its application in peptide design.
  Nucleic Acids Res, 37, D933-D937.  
19167304 J.T.Cheng, J.D.Hale, M.Elliot, R.E.Hancock, and S.K.Straus (2009).
Effect of membrane composition on antimicrobial peptides aurein 2.2 and 2.3 from Australian southern bell frogs.
  Biophys J, 96, 552-565.  
19581460 R.F.Epand, G.Wang, B.Berno, and R.M.Epand (2009).
Lipid segregation explains selective toxicity of a series of fragments derived from the human cathelicidin LL-37.
  Antimicrob Agents Chemother, 53, 3705-3714.  
17259271 Y.L.Pan, J.T.Cheng, J.Hale, J.Pan, R.E.Hancock, and S.K.Straus (2007).
Characterization of the structure and membrane interaction of the antimicrobial peptides aurein 2.2 and 2.3 from Australian southern bell frogs.
  Biophys J, 92, 2854-2864.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.