Rhodopsin-based models

Figure 8.1 Details of the intermolecular interactions from a minimized complex between norepinephrine and a rhodopsin-based model of the aib-AR are shown. As for the amino acid residues (D3.32, S5.42 and F6.51), only the polar hydrogen atoms are shown. Norepinephrine is colored by atom type, whereas the amino acid residues are colored according to their helix location.

The volumes were estimated as 1,620 and 1,930 A3, respectively, but they cannot be compared with the volume of the binding site of the rhodopsin-based model, which is closed and has a volume of 660 A3 (Fig. 8.5). 

Early experiments with bacteriorhodopsin (228) interpreted the Raman spectrum in terms of an unprotonated Schiff base, forming a charge-transfer complex with a protein functional group (210,212). This interpretation of the Raman data, essentially based on a comparison with the frequencies of model Schiff bases in solution, was criticized by Honig and Ebrey (48), who pointed out that consistency could also be obtained with a protonated Schiff base model. The latter hypothesis was subsequently confirmed by deuteration experiments similar to those described for rhodopsin (229,230), and by Raman spectra in denatured systems (231). In variance with the clear-cut similarity observed between the resonance-Raman spectra of rhodopsin and isorhodopsin, and those of the 11-cis and 9-cis model compounds, respectively,... 

Figure 4 [lower left]. Vicinity of the ribose moiety of NECA to hydrophilic residues of TM7 in the rhodopsin-based molecular model of the human A2A receptor [7]. Mutation to Ala of each of the residues shown in space filling form prevents the high affinity binding of [ HjCGS 21680. 

Fig. 15.4-4 Three ligand binding sites model for monoamine-related CPCRs illustrated by a rhodopsin-based 3D model of the 5-HTia receptor (left extracellular view right side view). We recently proposed a three binding site hypothesis for the molecular recognition of ligands at monoamine CPCRs by combining ...

With the double aim of reducing computational costs as well as of understanding the most basic constituents in photodynamics processes, it has been common to investigate model systems, which are supposed to be the minimal unit that can stiU reproduce the photodynamics observed in the complete molecule. In the following sections, we shall review three classes of molecules and their model systems (1) protonated Schiff bases, models for rhodopsin chro-mophores (2) heteroaromatic rings, models for nucleic acid bases and (3) formamide, model for peptide bonds. 

A number of diflFerent animal models of uveitis have been developed) including that induced by organ-specific ocular antigens such as retinal S-antigen, rhodopsin and lens protein (Wacker et al., 1977 Rao et al., 1979). Other models are based on the injection of proteins foreign to the host, such as intravitreal injections of albumin or 7-globulin (Zimmerman and Silverstein, 1959 Kaplan etal., 1979). More recently, a third group of models has been developed based on the injection of inflammatory mediators such as interleukins-1 and 2, and tumour necrosis factor (Bhattacherjee and Henderson, 1987 ... 

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 values of the 15N CP MAS chemical shift of Lys296 nitrogen bonded to retinal via the —C=N bond ( Schiff base) was equal to 155.4 ppm for rhodopsin and 282.8 ppm for metarhodopsin (relative to 5.6 M aqueous NH4C1).70 The results proved the imine bond polarisation, which facilitates Schiff base hydrolysis. The comparison between chemical shifts for metarhodopsin and model compounds suggested that Schiff base linkage of the all-frans retinal chromophore in Metall is in a polar environment. 

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