title: Alpha-retinals as rhodopsin chromophores--preference for the 9-Z configuration and partial agonist activity.
abstract: The visual pigment rhodopsin, the photosensory element of the rod photoreceptor cell in the vertebrate retina, shows in combination with an endogenous ligand, 11-Z retinal, an astonishing photochemical performance. It exhibits an unprecedented quantum yield (0.67) in a highly defined and ultrafast photoisomerization process. This triggers the conformational changes leading to the active state Meta(rhodopsin) II. Retinal is covalently bound to Lys-296 of the protein opsin in a protonated Schiff base. The resulting positive charge delocalization over the terminal part of the polyene chain of retinal creates a conjugation defect that upon photoexcitation moves to the opposite end of the polyene. Shortening the polyene as in 4,5-dehydro,5,6-dihydro (alpha), 5,6-dihydro or 7,8-dihydro-analogs might facilitate photoisomerization of a 9-Z and a 11-Z bond. Here we describe pigment analogs generated with bovine opsin and 11-Z or 9-Z 4,5-dehydro,5,6-dihydro-retinal that were further characterized by UV-Vis and FTIR spectroscopy. The preference of opsin for native 11-Z retinal over the 9-Z isomer is reversed in 4,5-dehydro,5,6-dihydro-retinal. 9-Z 4,5-dehydro,5,6-dihydro-retinal readily generated a photosensitive pigment. This modification has no effect on the quantum yield, but affects the Batho<-->blueshifted intermediate (BSI) equilibrium and leads to a strong decrease in the G-protein activation rate because of a downshift of the pK(a) of the Meta I<-->Meta II equilibrium.
authors.affiliation: Department of BioOrganic Photochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wang
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Bovee-Geurts
authors.forename: Johan
authors.initials: J
authors.lastname: Lugtenburg
authors.forename: Willem J
authors.initials: WJ
authors.lastname: DeGrip
mesh_terms: D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory; D012172:Retinaldehyde / Q000032:analysis*; D012243:Rhodopsin / Q000737:chemistry*; D013053:Spectrophotometry
chemical_list: D012243:Rhodopsin; D012172:Retinaldehyde