1F0D
Cecropin A(1-8)-magainin 2(1-12) in dodecylphosphocholine micelles
Summary for 1F0D
| Entry DOI | 10.2210/pdb1f0d/pdb |
| Related | 1D9J 1D9L 1D9M 1D9O 1D9P 1F0E 1F0F 1F0G 1F0H |
| Descriptor | CECROPIN A-MAGAININ 2 HYBRID PEPTIDE (1 entity in total) |
| Functional Keywords | helix-turn-helix, antimicrobial protein |
| Total number of polymer chains | 1 |
| Total formula weight | 2411.05 |
| Authors | Oh, D.,Shin, S.Y.,Lee, S.,Kim, Y. (deposition date: 2000-05-16, release date: 2000-06-14, Last modification date: 2024-10-30) |
| Primary citation | Oh, D.,Shin, S.Y.,Lee, S.,Kang, J.H.,Kim, S.D.,Ryu, P.D.,Hahm, K.S.,Kim, Y. 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, 2000 Cited by PubMed 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. PubMed: 11009597DOI: 10.1021/bi000453g PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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