1f0h: Difference between revisions

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Cecropin A(1-8)-magainin 2(1-12) A2 in dodecylphosphocholine micelles

OverviewOverview

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.

About this StructureAbout this Structure

1F0H is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

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., Oh D, Shin SY, Lee S, Kang JH, Kim SD, Ryu PD, Hahm KS, Kim Y, Biochemistry. 2000 Oct 3;39(39):11855-64. PMID:11009597

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-[[Image:1f0h.jpg|left|200px]]<br /><applet load="1f0h" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1f0h" />
 '''Cecropin A(1-8)-magainin 2(1-12) A2 in dodecylphosphocholine micelles'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-F0H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1F0H OCA].
+F0H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F0H OCA].
 ==Reference==
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 [[Category: Lee, S.]]
 [[Category: Oh, D.]]
-[[Category: Shin, S.Y.]]
+[[Category: Shin, S Y.]]
 [[Category: NH2]]
 [[Category: helix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 14:30:04 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:30 2008''