Similarity of Ca(2+)-bound conformations of morphine and Met-enkephalin: a computational study.
The conformations of the free and Ca(2+)-bound forms of morphine and Met-enkephalin were compared based on an earlier proposal that extracellular Ca2+ may dictate the bioactive conformations of peptide hormones and drugs. A Monte Carlo with energy minimization method was used to calculate Met-enkephalin in the absence and presence of Ca2+. The Ca(2+)-bound conformation of Met-enkephalin was found to have an overall shape that matched well with that of morphine. In contrast, the uncomplexed Met-enkephalin did not have such a match. The data suggest that a ternary association of the mu-receptor, its ligands and Ca2+ may be an initial process in the signal transduction mechanism of opioid peptides.
Department of Biochemistry, McMaster University, Hamilton, Ont., Canada.
B S
BS
Zhorov
V S
VS
Ananthanarayanan
D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D004563:Electrochemistry; D004744:Enkephalin, Methionine / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009020:Morphine / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D004744:Enkephalin, Methionine; D009020:Morphine; D002118:Calcium