PDBsum entry 1f0e

Antimicrobial protein

PDB id: 1f0e

Contents

Protein chain

19 a.a.

PDB id:

1f0e

Name:

Antimicrobial protein

Title:

Cecropin a(1-8)-magainin 2(1-12) modified gig to p in dodecylphosphocholine micelles

Structure:

Cecropin a-magainin 2 hybrid peptide. Chain: a. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence for this peptide is a hybrid of sequences which occur naturally in hyalophora cecropia (cecropia moth) and xenopus laevis (african clawed frog)

NMR struc:

20 models

Authors:

D.Oh,S.Y.Shin,S.Lee,Y.Kim

Key ref:

D.Oh et al. (2000). Role of the hinge region and the tryptophan residue in the synthetic antimicrobial peptides, cecropin A(1-8)-magainin 2(1-12) and its analogues, on their antibiotic activities and structures. Biochemistry, 39, 11855-11864. PubMed id: 11009597 DOI: 10.1021/bi000453g

Date:

16-May-00 Release date: 14-Jun-00

Protein chain

P01507  (CECA_HYACE) -  Cecropin-A from Hyalophora cecropia

Seq: 64 a.a.

Struc: 19 a.a.*

Protein chain

P11006  (MAGA_XENLA) -  Magainins from Xenopus laevis

Seq: 303 a.a.

Struc: 19 a.a.*

* PDB and UniProt seqs differ at 19 residue positions (black crosses)

DOI no: 10.1021/bi000453g

Biochemistry 39:11855-11864 (2000)

PubMed id: 11009597

Role of the hinge region and the tryptophan residue in the synthetic antimicrobial peptides, cecropin A(1-8)-magainin 2(1-12) and its analogues, on their antibiotic activities and structures.

D.Oh, S.Y.Shin, S.Lee, J.H.Kang, S.D.Kim, P.D.Ryu, K.S.Hahm, Y.Kim.

ABSTRACT

A 20-residue hybrid peptide CA(1-8)-MA(1-12) (CA-MA), incorporating residues 1-8 of cecropin A (CA) and residues 1-12 of magainin 2 (MA), has potent antimicrobial activity without toxicity against human erythrocytes. To investigate the effects of the Gly-Ile-Gly hinge sequence of CA-MA on the antibacterial and antitumor activities, two analogues in which the Gly-Ile-Gly sequence of CA-MA is either deleted (P1) or substituted with Pro (P2) were synthesized. The role of the tryptophan residue at position 2 of CA-MA on its antibiotic activity was also investigated using two analogues, in which the Trp2 residue of CA-MA is replaced with either Ala (P3) or Leu (P4). The tertiary structures of CA-MA, P2, and P4 in DPC micelles, as determined by NMR spectroscopy, have a short amphiphilic helix in the N-terminus and about three turns of alpha-helix in the C-terminus, with the flexible hinge region between them. The P1 analogue has an alpha-helix from Leu4 to Ala14 without any hinge structure. P1 has significantly decreased lytic activities against bacterial and tumor cells and PC/PS vesicles (3:1, w/w), and reduced pore-forming activity on lipid bilayers, while P2 retained effective lytic activities and pore-forming activity. The N-terminal region of P3 has a flexible structure without any specific secondary structure. The P3 modification caused a drastic decrease in the antibiotic activities, whereas P4, with the hydrophobic Leu side chain at position 2, retained its activities. On the basis of the tertiary structures, antibiotic activities, vesicle-disrupting activities, and pore-forming activities, the structure-function relationships can be summarized as follows. The partial insertion of the Trp2 of CA-MA into the membrane, as well as the electrostatic interactions between the positively charged Lys residues at the N-terminus of the CA-MA and the anionic phospholipid headgroups, leads to the primary binding to the cell membrane. Then, the flexibility or bending potential induced by the Gly-Ile-Gly hinge sequence or the Pro residue in the central part of the peptides may allow the alpha-helix in the C-terminus to span the lipid bilayer. These structural features are crucial for the potent antibiotic activities of CA-MA.