Protein Catalysis of the Retinal Subpicosecond Photoisomerization in the Primary Process of Bacteriorhodopsin Photosynthesis

Li, Song; El‐Sayed, Mostafa A.; Lanyi, Janos Κ.

doi:10.1126/science.261.5123.891

Cited by 163 publications

(250 citation statements)

References 45 publications

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“…It is seen that the placement of retinal inside the protein reduces the isomerization barrier governing the thermal isomerization of retinal around two (C 13 -C 14 , C 15 -N) double bonds, by about 20 kcal/mol. This result is in agreement with the common notion that the protein environment enhances the isomerizational transformations of in situ retinal [71,72]. However, the question arises whether the standard classical electrostatic models with their pairwise additive potentials describe the chromophore-protein interactions properly, or if the polarizing effect of the environment must be included.…”

Section: Modeling the Dark Adaptation Of Bacteriorhodopsinsupporting

confidence: 79%

“…It has been observed that modification of protein groups in the vicinity of the retinal Schiff base shifts considerably the bR absorption spectrum [69] and affects drastically the rates of both thermally- [70] and photo- [71,72] activated isomerization processes in bR. The experiments imply that the protein environment plays a crucial role in determining the physico-chemical properties of…”

Section: Quantum Chemistry Of In Situ Retinalmentioning

confidence: 90%

“…It has been observed that modification of protein groups in the vicinity of the retinal Schiff base shifts considerably the bR absorption spectrum [69] and affects drastically the rates of both thermally- [70] and photo- [71,72] [75,76,77]. At present, there exist a number of ab initio as well as semi-empirical techniques which try to account for the realistic atomic structure and charge distribution of the environment via explicit incorporation of protein (or solution) point charges in the electronic Hamiltonian of the quantum chemically treated substrate [78,79,80,81,82,83].…”

Section: Quantum Chemistry Of In Situ Retinalmentioning

confidence: 99%

See 2 more Smart Citations

Quantum Chemistry of in situ Retinal: Study of the Spectral Properties and Dark Adaptation of Bacteriorhodopsin

Logunov

Schulten

1996

Quantum Mechanical Simulation Methods for Studying Biological Systems

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1A combination of molecular dynamics and quantum chemistry techniques have been employed to study the electronic excitation and conformational potential surface of retinal in the binding site of bacteriorhodopsin (bR). The CASSCF(6,9)/6-31G level of ab initio calculations (within Gaussian92) has been used for the treatment of both the ground (S0) and excited (S1) states of retinal. Charges of all atoms in the protein are represented by spherical Gaussians and explicitly included in the electronic Hamiltonian of retinal. Spectral properties have been analyzed for the native bR pigment as well as for its D85N mutant.The calculated relative shift in the absorption maxima between the two pigments is in better agreement with experiment than the computed absolute parameters of the absorption line shapes. The dark adaptation processes in bacteriorhodopsin (which involves rotation around the 13-14 and the 15-N retinal double bonds) has been modelled by following the pre-defined reaction coordinate. Our simulations support the notion that the isomerization process is catalyzed by the protonation of an aspartic acid (Asp85) side group of bacteriorhodopsin. 2 IntroductionBacteriorhodopsin (bR) spans the cell membrane of Halobacterium halobium and functions as a light-driven proton pump. bR contains seven α-helices which enclose the prosthetic group, all-trans retinal, bound via a protonated Schiff base linkage to Lys-216. Figure 1a shows the chemical structure of retinal and its conventional numbering scheme. The bR structure is presented in Fig. 2a. Retinal absorbs light and undergoes a photoisomerization process; the thermal reversal of this reaction is coupled to transfer of a proton from the cytoplasmic side (top in Fig. 2a) to the extracellular side (bottom in Fig. 2a) of the protein.Recent reviews that discuss the structure and function of bR are [1,2,3,4,5,6,7]. Figure 1 here Bacteriorhodopsin accomplishes its function through a cyclic process initiated by absorption of a photon. This photon triggers an isomerization of retinal, which proceeds then through several intermediate states identified by their absorption spectra. An accepted kinetic scheme for this cycle is an unbranched series of intermediates, shown in Fig. 3. Photoisomerization occurs in the bR 568 → J 625 transition. During the L 550 → M 412 transition the Schiff base proton is transferred to Asp-85 and, subsequently, to the outside of the cell [8,9,10,11,12,13]. During the M 412 → N 520 transition, a proton is transferred to the Schiff base from Asp-96, which then takes up a proton from the cytoplasmic environment [13]. The reaction cycle is completed as the protein returns to bR 568 via the O 640 intermediate. Figure 2 here When bR is allowed to equilibrate in the dark, it converts within an hour to a 2:1 mixture containing 13-cis retinal and all-trans retinal bR [14]. The protein containing the 13-cis retinal isomer of bRis referred to as the dark adapted (DA) pigment of bR, bR 548 , which absorbs at 548 nm. bR 548 contains, actually, retinal in a 1...

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Section: Modeling the Dark Adaptation Of Bacteriorhodopsinsupporting

confidence: 79%

“…It has been observed that modification of protein groups in the vicinity of the retinal Schiff base shifts considerably the bR absorption spectrum [69] and affects drastically the rates of both thermally- [70] and photo- [71,72] activated isomerization processes in bR. The experiments imply that the protein environment plays a crucial role in determining the physico-chemical properties of…”

Section: Quantum Chemistry Of In Situ Retinalmentioning

confidence: 90%

“…It has been observed that modification of protein groups in the vicinity of the retinal Schiff base shifts considerably the bR absorption spectrum [69] and affects drastically the rates of both thermally- [70] and photo- [71,72] [75,76,77]. At present, there exist a number of ab initio as well as semi-empirical techniques which try to account for the realistic atomic structure and charge distribution of the environment via explicit incorporation of protein (or solution) point charges in the electronic Hamiltonian of the quantum chemically treated substrate [78,79,80,81,82,83].…”

Section: Quantum Chemistry Of In Situ Retinalmentioning

confidence: 99%

See 1 more Smart Citation

Quantum Chemistry of in situ Retinal: Study of the Spectral Properties and Dark Adaptation of Bacteriorhodopsin

Logunov

Schulten

1996

Quantum Mechanical Simulation Methods for Studying Biological Systems

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“…Remarkably, the photoisomerization of the same chromophore in any environment other than that of the natural protein scaffold is no longer specific and it is less efficient and slower (5), indicating the enzymatic role of the protein environment that enhances the speed and selectivity of the retinal isomerization. Site-directed mutagenesis has shown that charged amino acid residues closely interacting with the charged retinal moiety (Arg 82 , Asp 85 , Asp 212 ) largely influence the isomerization speed (6,7). Theoretical investigations of a retinal-like model compound (8) rationalize these findings in modeling how a chloride counterion affects the energetics and photoreactivity.…”

mentioning

confidence: 86%

Functional electric field changes in photoactivated proteins revealed by ultrafast Stark spectroscopy of the Trp residues

Léonard

Portuondo-Campa

Cannizzo

et al. 2009

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

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retinal proteins ͉ dipolar interactions ͉ tryptophan ͉ ultraviolet probe T he membrane protein bacteriorhodopsin (bR) is a proton pump, the biological activity of which is triggered by the absorption of light by the protonated retinal cofactor (1, 2). On light excitation, the retinal moiety undergoes an isomerization from 13-cis to all-trans that proceeds with very high speed (Ϸ0.5 ps) and large quantum efficiency (Ϸ0.64). In the excited Franck-Condon state, before isomerization, a large photoinduced charge translocation along retinal increases its dipole moment by as much as 10-30 D (3, 4). Remarkably, the photoisomerization of the same chromophore in any environment other than that of the natural protein scaffold is no longer specific and it is less efficient and slower (5), indicating the enzymatic role of the protein environment that enhances the speed and selectivity of the retinal isomerization. Site-directed mutagenesis has shown that charged amino acid residues closely interacting with the charged retinal moiety (Arg 82 , Asp 85 , Asp 212 ) largely influence the isomerization speed (6, 7). Theoretical investigations of a retinal-like model compound (8) rationalize these findings in modeling how a chloride counterion affects the energetics and photoreactivity. In addition, within the protein, the large photoinduced charge translocation along retinal is expected to induce a strong, ultrafast dielectric response of the full protein environment (9, 10), which could also participate in the enzymatic function by driving specifically the isomerization path to all-trans retinal. Besides, the exact nature of the driving force for the biological activity of the protein has long been (11) and still is a subject of intensive investigations. Hence, protein conformational changes similar to those observed in functional wild-type (WT) bR have been observed in artificial proteins with nonisomerizing retinal chromophores (12), suggesting that the initial charge translocation alone would activate the modified proteins. In the initial steps of the photocycle, the protein has to convert and store light energy, so as to drive the primary proton transfer from the protonated retinal to the Asp 85 counter ion, and successive proton transfer reactions via small conformational rearrangements of the protein. Several origins have been proposed and debated for the dominating driving force leading to the primary and subsequent proton transfers, among which are (i) energy storage in the strained geometry of the isomerized chromophore (13), and (ii) electrostatic energy storage (14), either mainly due to the modification by the isomerization of the electrostatic interactions between the protein and the donor/ acceptor pair (15), or to a light-induced charge separation between primary proton donor and acceptor (16).To investigate the light-induced electrostatic and/or dielectric modifications along or in the vicinity of retinal, we performed ultrafast absorption spectroscopy on the nearby tryptophan residues. Wild-type bR contains 8 try...

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“…Understanding the solution photochemistry is critical because it provides the standard against which one can quantify the steering role of the protein environment. Although steric (26,27) and electrostatic (28,29) considerations have been invoked to rationalize the bond selectivity observed in protein environments, they do not explain the solution data for photoisomerization of all-trans RPSB. Entropic considerations associated with the large amplitude motion of isomerization in a confined solution environment would erroneously predict 13-cis to be the favored product.…”

mentioning

confidence: 99%

The role of intersection topography in bond selectivity ofcis-transphotoisomerization

Ben‐Nun

Molnár

Schulten

et al. 2002

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

143

146

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Ab initio methods are used to characterize the ground and first excited state of the chromophore in the rhodopsin family of proteins: retinal protonated Schiff base. Retinal protonated Schiff base has five double bonds capable of undergoing isomerization. Upon absorption of light, the chromophore isomerizes and the character of the photoproducts (e.g., 13-cis and 11-cis) depends on the environment, protein vs. solution. Our ab initio calculations show that, in the absence of any specific interactions with the environment (e.g., discrete ordered charges in a protein), energetic considerations cannot explain the observed bond selectivity. We instead attribute the origin of bond selectivity to the shape (topography) of the potential energy surfaces in the vicinity of points of true degeneracy (conical intersections) between the ground and first excited electronic states. This provides a molecular example where a competition between two distinct but nearly isoenergetic photochemical reaction pathways is resolved by a topographical difference between two conical intersections.O ne of the simplest means to convert light into mechanical motion at the atomic scale is cis-trans photoisomerization, and it is widely used in photoactive proteins. Retinal protonated Schiff base (RPSB) is the best known biological chromophore, with five double bonds capable of undergoing photoisomerization. A long-standing question has been the mechanism that selects the isomerizing bond, particularly the role of the protein environment in ''steering'' reactivity. The availability of the structures of rhodopsin (1) and bacteriorhodopsin (2-5), coupled with characterization of RPSB solution-phase photochemistry (6-11), provides a unique opportunity to identify this mechanism. Conical intersections (CIs), geometries where two electronic states are truly degenerate, providing doorways from excited to ground electronic states, are widely believed to be important in photochemistry (12)(13)(14), and their role in photoinduced isomerization has been well documented (14-22). However, their role in bond torsion selectivity has yet to be established. In this paper, we show that the topography, or shape, around CIs determines this selectivity in RPSB. This direct connection between CI topography and photochemical selectivity has significant implications for understanding protein ''steering'' and the rational design of molecular optoelectronic devices.Investigations of the photochemistry of RPSB have established that the protein is not an idle spectator; quantum yield, selectivity, and time scales are all significantly different in solution and protein environments. In the protein environment, isomerization occurs exclusively around a single bond, e.g., 11-cis 3 all-trans in rhodopsin and all-trans 3 13-cis in bacteriorhodopsin. In contrast, illumination of the all-trans chromophore in solution results in several photoproducts with 11-cis being the most dominant (6-8). The isomerization quantum yield is greater than 50% in proteins (23), but rarely excee...

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Protein Catalysis of the Retinal Subpicosecond Photoisomerization in the Primary Process of Bacteriorhodopsin Photosynthesis

Cited by 163 publications

References 45 publications

Quantum Chemistry of in situ Retinal: Study of the Spectral Properties and Dark Adaptation of Bacteriorhodopsin

Quantum Chemistry of in situ Retinal: Study of the Spectral Properties and Dark Adaptation of Bacteriorhodopsin

Functional electric field changes in photoactivated proteins revealed by ultrafast Stark spectroscopy of the Trp residues

The role of intersection topography in bond selectivity ofcis-transphotoisomerization

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