Opsin retinal binding

The fate of intracellular retinol is dependent on cell type. In the eye, trans-retinol can be esterified by LRAT or isomerized to ll-a>-ret-inol by a cell-specific isomerase (22). 11-cis-retinol is then oxidized to 11-cis-retinal by 11-cis-retinol dehydrogenase (22). 11-cis-retinal binds to opsin by forming a Schiff base with an opsin lysine residue and the resulting complex is known as rhodopsin (22). Rhodopsin is a member of the seven transmembrane family of proteins that serves as receptor for photons... 

The 11-CM retinal binds to opsin via the reaction between its aldehyde functional gronp (at the end of the carbon chain) and an amino group of lysine on the protein ... 

The all-fran retinal does not fit into the 11-cm retinal binding site on opsin therefore, npon isomerization the trans isomer separates from the protein. At this point an electrical impulse is generated and transmitted to the brain. In the absence of light, enzymes mediate the isomerization of all-fran retinal back to 11-cm retinal, and rhodopsin is regenerated by the binding of the cis isomer to opsin, as described above. With the completion of this step, the vision cycle can begin again. 

Vitamin A helps maintain the skin and mucous membranes of the oral cavity and the digestive, respiratory, reproductive, and urinary tracts. Vitamin A is also critical for vision. The aldehyde form of Vitamin A, called retinal, binds to a protein called opsin to form the visual pigment rhodopsin. This pigment is found in the rod cells of the retina of the eye. These cells are responsible for black-and-white vision. As you might expect, a deficiency of vitamin A can have terrible consequences. In children, lack of vitamin A leads to xerophthalmia, an eye disease that results first in night blindness and eventually in total blindness. The disease can be prevented by an adequate dietary or supplementary supply of this vitamin. Because vitamin A is stored in the liver, a dose of 0.03 mg will protect a child for six months. Yet in countries that have suffered from cruel famines, even this amount of vitamin A is unavailable, and the burdens of malnutrition and disease lead to total blindness in thousands of children. 

Reeves, P. J., Hwa, J., Khorana, H. G. (1999). Structure and function in rhodopsin Kinetic studies of retinal binding to purified opsin mutants in defined phosphohpid-detergent mixmres serve as probes of the retinal binding pocket. Proceedings of the National Academy of Sciences of the United States of America, 96, 1927—1931. 

This is the intermediate metabolite between retinol and tRA and is used in the visual cycle where 11 -cis-retinal binds with the protein opsin to form rhodopsin, the visual pigment. It is undetectable in mammalian and chick embryos, but present at very high levels in amphibian (11,12) and zebrafish eggs (13). It is not active in inducing pattern duplication in the regenerating amphibian limb (8). 

The retinal binds to the opsin protein by a protonated Schiff base. Through site-directed mutagenesis, the counterion for the Schiff base has been shown to be the glutamate residue at... 

Isralewitz et eil., 1997] Isralewitz, B., Izrailev, S., and Schulten, K. Binding pathway of retinal to bacterio-opsin A prediction by molecular dynamics simulations. Biophys. J. 73 (1997) 2972-2979... 

Rhodopsin is a seven ot-helix trans-membrane protein and visual pigment of the vertebrate rod photoreceptor cells that mediate dim light vision. In this photoreceptor, retinal is the chromophore bound by opsin protein, covalently linked to Lys296 by a Schiff base linkage. Kpega et al.64 have studied NMR spectra of Schiff bases being derivatives of all-frans retinal and amino-p-cyclodextrins as a model of rhodopsin, where p-cyclodextrin plays a role of a binding pocket. On the basis of analysis of the chemical shift differences for the model compound in the presence and in the absence of adamantane carboxylate, it has been shown that the derivative of 3-amino-p-cyclodextrin forms dimer in water and retinoid is inserted into p-cyclodextrin cavity [31]. 

The evidence to-date shows that vertebrate photoreception is mediated by a closely related group of proteins termed opsins. These are G protein-coupled receptors characterized by their ability to bind a vitamin A based chromophore ( -cis-retinal) via a Schiff base linkage using a lysine residue in the 7th transmembrane a helix (Fig. 1). The primary events of image detection by the rods and cones occurs with the absorption of a photon of light by ll-r/r-retinal and its photoisomerization to the AUtrans state (Bums Baylor 2001, Menon et al 2001). Although photoreception is best understood in retinal rods and cones, photoreception is not confined to these structures. In non-mammalian... 

In a crystal structure47111-ds-retinal has the 12-s-cis conformation shown at the top in Eq. 23-36 rather than the 12-s-frans conformation at the center and in which there is severe steric hindrance between the 10-H and 13-CH3. Nevertheless, H-and 13C-NMR spectroscopy suggest that the retinal in rhodopsin is in a twisted 12-s-frans conformation.472 4723 The Schiff base of 11-ds-retinal with N-butylamine has an absorption maximum at -360 nm but N-protonation, as in the structure in Eq. 23-36, shifts the maximum to 440 nm with emax = 40,600 M 1 cm 1 (Fig. 23-42). This large shift in the wavelength of the absorption maximum (the opsin shift) indicates that binding to opsin stabiliz-... 

A mathematical model of the putative binding of retinal to a lysine group at location 296 in opsin also appeared in 198996. Such a location would suggest a formulation such as 296, (N-retiny 1-ly sinejopsin. No laboratory confirmation of either model of a retinene attached to opsin through a Schiff-base has appeared. 

Optical activity is induced by the protein, since upon binding of the retinal to opsin, the retinylidene chromophore could become inherently chiral [64-67],... 

---