PDBsum entry 2e3e

Antimicrobial protein

PDB id: 2e3e

Contents

Protein chain

45 a.a. *

* Residue conservation analysis

PDB id:

2e3e

Name:

Antimicrobial protein

Title:

Nmr structure of def-bbb, a mutant of anopheles defensin def-aaa

Structure:

Defensin, mutant def-bbb. Chain: a. Fragment: residues 63-102. Engineered: yes

Source:

Anopheles gambiae. African malaria mosquito. Organism_taxid: 7165. Gene: def1. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.

NMR struc:

9 models

Authors:

C.Landon,F.Barbault,F.Vovelle

Key ref:

C.Landon et al. (2008). Rational design of peptides active against the gram positive bacteria Staphylococcus aureus. Proteins, 72, 229-239. PubMed id: 18214975 DOI: 10.1002/prot.21912

Date:

22-Nov-06 Release date: 13-Nov-07

Protein chain

Q17027  (DEFI_ANOGA) -  Defensin from Anopheles gambiae

Seq: 102 a.a.

Struc: 45 a.a.*

* PDB and UniProt seqs differ at 18 residue positions (black crosses)

DOI no: 10.1002/prot.21912

Proteins 72:229-239 (2008)

PubMed id: 18214975

Rational design of peptides active against the gram positive bacteria Staphylococcus aureus.

C.Landon, F.Barbault, M.Legrain, M.Guenneugues, F.Vovelle.

ABSTRACT

In an attempt to increase the antimicrobial activity of the insect defensin from Anopheles gambiae, which is active against Staphylococcus aureus at low concentration, hybrid defensins were designed by combining conserved sequence regions and variable regions of insect defensins. Their activity against S. aureus strains sensitive and resistant to conventional antibiotics was evaluated, and the toxicity of the most active molecules was tested. The three-dimensional structure of Anopheles gambiae defensin and five hybrids were determined by NMR and molecular modelling. This strategy led to the design of two chimeric defensins with increased activity compared with the native molecule, but one of them appears to be toxic to mice at a rather low concentration. The structure of the CS alphabeta motif, which is a characteristic of insect defensin, is sensitive to sequence modifications, in particular in the N-terminal loop. The existence of the CS alphabeta is most probably a prerequisite for the stability and the activity of the molecule, but is not sufficient by itself since the hybrid displaying the best defined structure is not active against the tested strains. The analysis of the structure, in relation with the activity and the toxicity data, underlines the importance of turns and of the N-terminal loop. Residues located in the turns contributing to the preservation of positive electrostatic areas at the surface of the molecules seem particularly important for the activity of the molecule, while residues involved in the N-terminal loop are both involved in the modulation of the activity and the toxicity of the molecule.

Selected figure(s)

Figure 2.
Figure 2. Superposition of the 10 best models for each hybrid defensin.

Figure 3.
Figure 3. Hydrophobic and electrostatic potentials at the surface of the defensins. First panel: Def-AAA, Def-ABB, and Def-AcAA; second panel: Def-BAT, Def-BBB, and Def-DAA. Two orientations are shown. For each orientation, from the left to the right: the global fold, the hydrophobic potentials and the electrostatic potentials are represented. For the electrostatic potential, cationic poles are coloured in red-brown, anionic regions are in blue, and neutral regions are in green. For the hydrophobic potential, hydrophobic regions are in brown, hydrophilic one in blue and intermediate regions are in green.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 72, 229-239) copyright 2008.

Figures were selected by the author.