Conformational features responsible for the binding of cyclic analogues of enkephalin to opioid receptors. II. Models of mu- and delta-receptor-bound structures for analogues containing Phe4.
Models of mu- and delta-receptor-bound backbone conformations of enkephalin cyclic analogues containing Phe4 were determined by comparing geometrical similarity among the previously found low-energy backbone structures of [D-Cys2,Cys5]-enkephalinamide, [D-Cys2,D-Cys5]-enkephalinamide, [D-Pen2,L-Pen5]-enkephalin and [D-Pen2,D-Pen5]-enkephalin. The present mu-receptor-bound conformation resembles a beta-I bend in the peptide backbone centred on the Gly3-Phe4 region. Two slightly different models were found for the delta-receptor-bound conformation; both of them are more extended than the mu-receptor-bound conformation and include a gamma-turn (or a gamma-like turn) on the Gly3 residue. Energetically favourable rotamers of Tyr and Phe side chains were also determined for the mu- and delta-conformations. The present models of mu- and delta-conformations share geometrical similarity with the low-energy structures of Leu-enkephalin and the Tyr-D-Lys-Gly-Phe-analogue.
Nikiforovich
G V
GV
Institute of Organic Synthesis, Latvian SSR Academy of Sciences, Riga.
Golbraikh
A A
AA
Shenderovich
M D
MD
Balodis
J
J
D000595:Amino Acid Sequence; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu