Contribution of proline-14 to the structure and actions of melittin.
The structure and dynamic properties of bee venom melittin and a synthetic analogue, [Ala14]-melittin (melittin P14A), are compared, using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy and amide exchange measurements in methanol. P14A is shown to adopt a regular, stable alpha-helical conformation in solution without the flexibility around the Pro-14 residue found in melittin. P14A has twice the hemolytic activity of melittin but is less able to induce voltage-dependent ion conductance in planar bilayers. The results indicate that helix flexibility afforded by the Pro-14 residue promotes the ability of melittin to adopt the transbilayer associates thought to underlie ion translocation.
Dempsey
C E
CE
Biochemistry Department, Oxford University, UK.
Bazzo
R
R
Harvey
T S
TS
Syperek
I
I
Boheim
G
G
Campbell
I D
ID
D000409:Alanine; D000595:Amino Acid Sequence; D004553:Electric Conductivity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008555:Melitten / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011392:Proline; D011487:Protein Conformation
D008051:Lipid Bilayers; D008555:Melitten; D011392:Proline; D000409:Alanine