An external point-charge model for wavelength regulation in visual pigments

Honig, Barry; Dinur, U.; Nakanishi, Kōji; Balogh‐Nair, Valeria; Gawinowicz, Mary Ann; Arnaboldi, Maria; Motto, Michael G.

doi:10.1021/ja00517a060

Cited by 354 publications

(216 citation statements)

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“…The quality of the used quantum chemical method has also allowed to reproduce the difference between the absorption maximum ( max a ) of Rh and of its retinal chromophore in methanol solution (i.e., the so called opsin-shift; ref. 15) with a Ͻ2 kcal⅐mol Ϫ1 error (see also Fig. 2A).…”

mentioning

confidence: 89%

The color of rhodopsins at theab initiomulticonfigurational perturbation theory resolution

Coto

Strambi

Ferré

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

131

204

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We demonstrate that ''brute force'' quantum-mechanics͞molecu-lar-mechanics computations based on ab initio (i.e., first principles) multiconfigurational perturbation theory can reproduce the absorption maxima of a set of modified bovine rhodopsins with an accuracy allowing for the analysis of the factors determining their colors. In particular, we show that the theory accounts for the changes in excitation energy even when the proteins display the same charge distribution. Three color-tuning mechanisms, leading to changes of close magnitude, are demonstrated to operate in these conditions. The first is based on the change of the conformation of the conjugated backbone of the retinal chromophore. The second operates through the control of the distance between the positive charge residing on the chromophore and the carboxylate counterion. Finally, the third mechanism operates through the changes in orientation of the chromophore relative to the protein. These results offer perspectives for the unbiased computational design of mutants or chemically modified proteins with wanted optical properties.excited states ͉ quantum mechanics͞molecular mechanics R ecently, protein mutants displaying properties such as high binding affinities and novel catalytic activities (1, 2) have been designed by using computational methods based on molecular mechanics. In a close context, substrate selectivity has been simulated by using more advanced tools based on density functional theory and molecular mechanics paving the way to the design of mutations that convert receptors into enzymes (3). However, the design of mutants with specific spectral properties, such as color and luminescence, represents a more complex problem. In these cases, the quantum chemical method used must be capable to describe both ground and electronically excited states of the protein chromophore. The ab initio (i.e., first-principles) complete-active-space self-consistent-field (CASSCF) method (4) is a multiconfigurational method offering maximum flexibility for an unbiased description of the electronic and equilibrium structure of a molecule (i.e., with no empirically derived parameters and avoiding single-reference wavefunctions). Furthermore, the CASSCF wave function can be used for subsequent multiconfigurational second-order perturbation theory (5) computations (CASPT2) of the dynamic correlation energy of each state ultimately leading to a nearly quantitative evaluation of the excitation energies of organic compounds (6, 7). The CASPT2 ability to describe exotic bonding has been recently assessed (8).In a previous study (9), we implemented the ab initio CASPT2͞͞CASSCF protocol (where equilibrium geometries and electronic energies are determined at the CASSCF and CASPT2 levels, respectively) in a quantum mechanics͞ molecular mechanics (QM͞MM) scheme (10-12) allowing for the evaluation of the excitation energy of chromophores (treated quantum mechanically) embedded in a protein environment (described by a MM force field).The absorption and fluorescence max...

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mentioning

confidence: 89%

The color of rhodopsins at theab initiomulticonfigurational perturbation theory resolution

Coto

Strambi

Ferré

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

131

204

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“…22 to four possible configurations. The distance of C 12 to O 1 of Glu-113 was taken to be Ϸ3 Å (6,7,41).…”

Section: Scheme IIImentioning

confidence: 99%

“…4a, are shown as well. The distance of the Glu-113 oxygen closest to C12 (referred to as O1) was kept at 3 Å in rho and in batho (7,41). It is likely that structural water forms a hydrogen bond network from O2 of Glu-113 to the SB proton (white) (not shown in this figure) (7,42).…”

Section: Scheme IIImentioning

confidence: 99%

Chromophore structural changes in rhodopsin from nanoseconds to microseconds following pigment photolysis

Jäger

Lewis

Zvyaga

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Rhodopsin is a prototypical G proteincoupled receptor that is activated by photoisomerization of its 11-cis-retinal chromophore. Mutant forms of rhodopsin were prepared in which the carboxylic acid counterion was moved relative to the positively charged chromophore Schiff base. Nanosecond time-resolved laser photolysis measurements of wild-type recombinant rhodopsin and two mutant pigments then were used to determine reaction schemes and spectra of their early photolysis intermediates. These results, together with linear dichroism data, yielded detailed structural information concerning chromophore movements during the first microsecond after photolysis. These chromophore structural changes provide a basis for understanding the relative movement of rhodopsin's transmembrane helices 3 and 6 required for activation of rhodopsin. Thus, early structural changes following isomerization of retinal are linked to the activation of this G protein-coupled receptor. Such rapid structural changes lie at the heart of the pharmacologically important signal transduction mechanisms in a large variety of receptors, which use extrinsic activators, but are impossible to study in receptors using diffusible agonist ligands.Rhodopsin is the light-triggered membrane receptor in rod outer segments responsible for dim-light vision. Absorption of light transforms rhodopsin (rho) into an activated state, which interacts with a heterotrimeric G protein to initiate an enzyme cascade leading to visual transduction. To reach this active state, called metarhodopsin (meta) II (1, 2), rho passes through a number of intermediates that have been characterized by UV-visible, Fourier-transform infrared (FTIR), Raman, and NMR spectroscopies, in addition to spin-labeling and biochemical studies (3-10). One way to characterize the intermediates is to trap them at low temperatures. This approach led to the classical ''bleaching'' scheme ( max values in nanometers): rho (498) 3 bathorhodopsin (batho) (542) 3 lumirhodopsin (lumi) (497) 3 meta I (480) 3 meta II (380) Scheme I However, at more physiologically relevant temperatures, time-resolved measurements up to 1 msec after photolysis reveal a new intermediate and a different kinetic scheme (3, 11). The following reaction scheme was proposed to occur during the nanosecond-to-microsecond time regime (3): rho (498) 3 batho (529) ª bsi (477) 3 lumi (492) 3 . . . Scheme II The new intermediate, blue-shifted intermediate of rho (bsi), is entropically favored and thus not trapped at low temperatures (11).The role of various structural features of the retinal chromophore in early rho photointermediates has been studied through time-resolved spectral measurements of artificial rho, in which the native chromophore is replaced by synthetically modified retinals (12). In studies of bacteriorhodopsin, timeresolved absorption spectroscopy has been shown to be particularly valuable when combined with site-directed mutagenesis to probe the roles of specific protein residues in different intermediates (13). Unti...

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“…Empirical and theoretical studies of the spectral tuning in organic solvents have suggested several mechanisms. They include the following: (i) an alteration in the strength of the electrostatic interaction between the protonated Schiff base and its counter ion or hydrogen bond acceptor (8 -10); (ii) an alteration in the polarity or polarizability of the environment of the chromophore-binding site, caused by the arrangement of polar or aromatic residues (10,11); and (iii) an isomerization around the 6-S bond (6,7-torsion angle) connecting the polyene chain to the ␤-ionone ring (9,10,12). By the combinations of these effects, microbial (type 1) rhodopsins show various absorption maxima ranging from 485 to 590 nm.…”

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confidence: 99%

Spectral Tuning in Sensory Rhodopsin I from Salinibacter ruber

Sudo

Yuasa

Shibata

et al. 2011

Journal of Biological Chemistry

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Organisms utilize light as energy sources and as signals. Rhodopsins, which have seven transmembrane ␣-helices with retinal covalently linked to a conserved Lys residue, are found in various organisms as distant in evolution as bacteria, archaea, and eukarya. One of the most notable properties of rhodopsin molecules is the large variation in their absorption spectrum. Sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII) function as photosensors and have similar properties (retinal composition, photocycle, structure, and function) except for their max (SRI, ϳ560 nm; SRII, ϳ500 nm). An expression system utilizing Escherichia coli and the high protein stability of a newly found SRI-like protein, SrSRI, enables studies of mutant proteins. To determine the residue contributing to the spectral shift from SRI to SRII, we constructed various SRI mutants, in which individual residues were substituted with the corresponding residues of SRII. Three such mutants of SrSRI showed a large spectral blue-shift (>14 nm) without a large alteration of their retinal composition. Two of them, A136Y and A200T, are newly discovered color tuning residues. In the triple mutant, the max was 525 nm. The inverse mutation of SRII (F134H/Y139A/ T204A) generated a spectral-shifted SRII toward longer wavelengths, although the effect is smaller than in the case of SRI, which is probably due to the lack of anion binding in the SRII mutant. Thus, half of the spectral shift from SRI to SRII could be explained by only those three residues taking into account the effect of Cl ؊ binding.

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An external point-charge model for wavelength regulation in visual pigments

Cited by 354 publications

References 0 publications

The color of rhodopsins at theab initiomulticonfigurational perturbation theory resolution

The color of rhodopsins at theab initiomulticonfigurational perturbation theory resolution

Chromophore structural changes in rhodopsin from nanoseconds to microseconds following pigment photolysis

Spectral Tuning in Sensory Rhodopsin I from Salinibacter ruber

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