PDBsum entry: 1vm5

Antibiotic

PDB-id: 1vm5

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14 a.a.

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• 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.
• Resolution: not givenÅ
• NMR structure: 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
• Related entries: 1o53 ; nmr structure of the membrane anchor ; 1vm2 ; 1vm3 ; 1vm4

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Key reference

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.