A rhodopsin-based model for melatonin recognition at its G protein-coupled receptor.
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A rhodopsin-based model for melatonin recognition at its G protein-coupled receptor. / Navajas, C; Kokkola, Tarja; Poso, A; Honka, N; Gynther, J; Laitinen, J T.
In: EUR J PHARMACOL, Vol. 304, No. 1-3, 1-3, 1996, p. 173-183.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A rhodopsin-based model for melatonin recognition at its G protein-coupled receptor.
AU - Navajas, C
AU - Kokkola, Tarja
AU - Poso, A
AU - Honka, N
AU - Gynther, J
AU - Laitinen, J T
PY - 1996
Y1 - 1996
N2 - The recent elucidation of the primary structures of different melatonin receptors as well as the deduction of the secondary structure of rhodopsin has allowed us to construct a model for melatonin recognition at its G protein-coupled receptor. To achieve this, we have used the quantum mechanics method Austin model 1 to fully optimize the structures of melatonin and several analogs. We also synthesized three compounds and used the three-dimensional analysis comparative molecular field analysis (CoMFA) to generate a model for the structure-activity relationships of melatonin and 27 melatonin-like compounds. This model predicted with good accuracy the affinities of the synthesized compounds for the melatonin receptor. We propose that recognition of the functional moieties of melatonin occurs through specific interaction of these moieties with fully conserved amino acid residues present in transmembrane helices V, VI and VII of the melatonin receptor. These residues are not found in other members of the G protein-coupled receptor family. The rhodopsin-based model can explain the importance of some structural features of melatonin and related active compounds.
AB - The recent elucidation of the primary structures of different melatonin receptors as well as the deduction of the secondary structure of rhodopsin has allowed us to construct a model for melatonin recognition at its G protein-coupled receptor. To achieve this, we have used the quantum mechanics method Austin model 1 to fully optimize the structures of melatonin and several analogs. We also synthesized three compounds and used the three-dimensional analysis comparative molecular field analysis (CoMFA) to generate a model for the structure-activity relationships of melatonin and 27 melatonin-like compounds. This model predicted with good accuracy the affinities of the synthesized compounds for the melatonin receptor. We propose that recognition of the functional moieties of melatonin occurs through specific interaction of these moieties with fully conserved amino acid residues present in transmembrane helices V, VI and VII of the melatonin receptor. These residues are not found in other members of the G protein-coupled receptor family. The rhodopsin-based model can explain the importance of some structural features of melatonin and related active compounds.
M3 - SCORING: Zeitschriftenaufsatz
VL - 304
SP - 173
EP - 183
JO - EUR J PHARMACOL
JF - EUR J PHARMACOL
SN - 0014-2999
IS - 1-3
M1 - 1-3
ER -