Conformational analysis of the Ca(2+)-bound opioid peptides: implications for ligand-receptor interaction.
Based on our earlier proposal on the role of Ca2+ in ligand-receptor recognition and the demonstration of the similarity of the Ca(2+)-bound forms of Met-enkephalin and morphine (Zhorov, B.S. and Ananthanarayanan, V.S., FEBS Lett. 354, 131-134 (1994)) we have undertaken the conformational analysis of a series of the Ca(2+)-bound opioid peptides aiming to find their conformations matching Ca(2+)-bound morphine. A Monte Carlo-with-energy-minimization method was used to calculate 14 opioid peptides in the presence of Ca2+. Low-energy conformations of the Ca2+ complexes of peptides with high mu-affinity were found to resemble closely morphine-Ca2+ complex. In contrast, the Ca2+ complexes of peptides with low mu-affinity did not. The results are relevant for understanding the structure-activity relations of opioid receptor ligands.
Zhorov
B S
BS
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Ananthanarayanan
V S
VS
D000595:Amino Acid Sequence; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D009020:Morphine / Q000737:chemistry / Q000378:metabolism; D018847:Opioid Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017450:Receptors, Opioid, mu / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008024:Ligands; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D009020:Morphine; D002118:Calcium