Zhorov B S, Ananthanarayanan V S
Department of Biochemistry, McMaster University, Hamilton, Ont., Canada.
FEBS Lett. 1994 Nov 7;354(2):131-4. doi: 10.1016/0014-5793(94)01071-4.
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.
