52647-48-0Relevant articles and documents
Mechanism of Retinal Schiff Base Formation and Hydrolysis in Relation to Visual Pigment Photolysis and Regeneration: Resonance Raman Spectroscopy of a Tetrahedral Carbinolamine Intermediate and Oxygen-18 Labeling of Retinal at the Metarhodopsin Stage in Photoreceptor
Cooper, Alan,Dixon, Sheila F.,Nutley, Margaret A.,Robb, Jenifer L.
, p. 7254 - 7263 (1987)
The mechanism of formation and hydrolysis of N-retinylidene-n-butylamine, as a model of the rhodopsin chromophore, has been investigated by a study of the kinetic and equilibrium properties in aqueous anionic, cationic, and neutral detergent micelle systems.The pH dependence of steady-state formation and hydrolysis rate constants is consistent with the classical imine reaction mechanism involving tetrahedral carbinolamine intermediates.Kinetic transients consistent with such intermediates can be seen using rapid stopped-flow techniques.Hydrolysis rates in neutral detergent micelles exhibit general base catalysis, and there are pronounced detergent-specific effects which can be qualitatively interpreted in terms of ionic effects on Schiff base pKa and micellar hydrogen ion activities.This suggests a rational explanation for the anomalous pKa and thermodynamic stability of visual pigment chromophores under physiological conditions.The tetrahedral intermediate has been observed directly at room temperature by continuous-flow, pH-jump resonance Raman spectroscopy, and the spectrum of this transient species shows remarkable similarity with the previously reported Raman spectrum of the metarhodopsin II intermediate of bovine rhodopsin photolysis.Isotope-labeling experiments on bovine photoreceptor membranes exposed to oxygen-18 enriched water during bleaching show incorporation of 18O at the retinal aldehyde site during the metarhodopsin I -> II transition.These observations support the hypothesis that the vertebrate Meta I -> Meta II transition involves hydrolytic attack by water on the retinyl-lysine Schiff base linkage of the rhodopsin chromophore.
6-s-cis conformation and polar binding pocket of the retinal chromophore in the photoactivated state of rhodopsin
Ahuja, Shivani,Eilers, Markus,Hirshfeld, Amiram,Yan, Elsa C. Y.,Ziliox, Martine,Sakmar, Thomas P.,Sheves, Mordechai,Smith, Steven O.
experimental part, p. 15160 - 15169 (2010/01/29)
The visual pigment rhodopsin is unique among the G protein-coupled receptors in having an 11-cis retinal chromophore covalently bound to the protein through a protonated Schiff base linkage. The chromophore locks the visual receptor in an inactive conformation through specific steric and electrostatic interactions. This efficient inverse agonist is rapidly converted to an agonist, the unprotonated Schiff base of all-trans retinal, upon light activation. Here, we use magic angle spinning NMR spectroscopy to obtain the 13C chemical shifts (C5-C20) of the all-trans retinylidene chromophore and the 15N chemical shift of the Schiff base nitrogen in the active metarhodopsin II intermediate. The retinal chemical shifts are sensitive to the conformation of the chromophore and its molecular interactions within the protein-binding site. Comparison of the retinal chemical shifts in metarhodopsin II with those of retinal model compounds reveals that the Schiff base environment is polar. In particular, the 13C15 and 15Nε chemical shifts indicate that the CdN bond is highly polarized in a manner that would facilitate Schiff base hydrolysis. We show that a strong perturbation of the retinal 13C12 chemical shift observed in rhodopsin is reduced in wild-type metarhodopsin II and in the E181Q mutant of rhodopsin. On the basis of the T1 relaxation time of the retinal 13C18 methyl group and the conjugated retinal 13C5 and 13C8 chemical shifts, we have determined that the conformation of the retinal C6-C7 single bond connecting the β-ionone ring and the retinylidene chain is 6-s-cis in both the inactive and the active states of rhodopsin. These results are discussed within the general framework of ligand-activated G protein-coupled receptors.
Constitution and stabilisation of retinal schiff bases in phosphatidylcholine liposomes
Singh, Anil K.,Das, Joydip
, p. 187 - 194 (2007/10/03)
All-trans-retinal (1) intercalated in lecithin liposomes reacts with n-butylamine yielding the all-trans-N-retinylidene-n-butylamine (2). The rate of formation of 2 in liposomes is approximately 5-6 times slower as compared to the rate in aqueous buffer (
