The different influences of ether and ester phospholipids on the conformation of gramicidin A. A molecular modelling study.
With AMBER (assisted model building with energy refinement) molecular modelling techniques, the interactions between lipids which differ in the type of chain linkage (e.g., ether or ester) and gramicidin were approximated. It was found, theoretically, that replacement of the ester function in dipalmitoylphosphatidylcholine (DPPC) by an ether moiety induces a shift in the rotameric distribution of the Trp-15 side-chain in gramicidin A. Concomitantly, the channel entrance is contracted by approx. 0.4 A. The perturbation can be related to the strong hydrogen-bond formed between the lipid carbonyl group and the indole proton of the Trp-15 residue of gramicidin. In the ether lipid-gramicidin assembly a weaker H-bond is formed between Trp-15 and the phosphate moiety. To obtain a first indication of the influence of the strength of this H-bond on gramicidin A, a preliminary experimental study was set up. The transport properties of gramicidin A were studied using efflux measurements through vesicle walls containing ether and ester lipids, respectively. A change in the permeability of gramicidin A was found when ether lipids were added to a bilayer composed of the ester lipid dioleoylphosphatidylcholine (DOPC).
Meulendijks
G H
GH
Department of Organic Chemistry, Eindhoven University of Technology, The Netherlands.
Sonderkamp
T
T
Dubois
J E
JE
Nielen
R J
RJ
Kremers
J A
JA
Buck
H M
HM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology*; D003198:Computer Simulation; D004952:Esters / Q000494:pharmacology*; D004987:Ethers / Q000494:pharmacology*; D006096:Gramicidin; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010539:Permeability; D010713:Phosphatidylcholines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D014364:Tryptophan
D002264:Carboxylic Acids; D004952:Esters; D004987:Ethers; D010713:Phosphatidylcholines; D010743:Phospholipids; D006096:Gramicidin; D015060:1,2-Dipalmitoylphosphatidylcholine; D014364:Tryptophan; D012964:Sodium; C017251:1,2-oleoylphosphatidylcholine