@article{f4ae49d272224f108ae79a8b2959d5a1,
title = "Substituents at the C13 Position of Retinal and Their Influence on the Function of Bacteriorhodopsin",
abstract = "Retinal analogues in which the 13-methyl group is replaced by H, C2H5, CF3, and OCH3 residues are studied by means of quantumchemical modified neglect of diatomic overlap-correlated version (MNDOC) calculations. The analogues are suitable to test the stereochemical mechanism of proton pumping in bacteriorhodopsin. The results explain the proton-pumping activities of bacterio-opsin reconstituted with these analogues and elucidate the decisive role of retinal's ground-state intramolecular properties in the pump cycle of bacteriorhodopsin.",
author = "Paul Tavan and Klaus Schulten and Wolfgang G{\"a}rtner and Dieter Oesterhelt",
note = "Funding Information: The explanation of the observations on the artifical BR chromophore reconstituted from 13-methoxyl-retinal in terms of the intramolecular properties of the corresponding RSBH+ is corroborated by chromophore reconstitution experiments with 9-cis 9-methoxy-retinal. As is well known, no 9-cis isomer of retinal flts into BR's binding site (22). Correspondingly, a mixture of 9-cis 9-methoxy- retinal with bacterio-opsin absorbs at 410 nm, a spectral position that indicates that no protonated Schiff-base linkage has been formed. Light-induced isomerization around the 9-10 double bond leads to the formation of a 560-nm chromophore containing the all-trans isomer. This chromophore is thermally unstable and decays to the 410-nm mixture containing the 9-cis configuration of the derivative (Gartner, W., and D. Oesterhelt, manuscript in preparation). This behavior is explained by the data in Table IV, which demonstrate that the all-trans state of 9-OCH3-RET-NH' is thermally unstable with respect to an all-trans 9-cis isomerization in contrast to the properties of the corresponding 9-methyl RSBH+. SUMMARY We have demonstrated on the basis of quantumchemical MNDOC calculations in how far the ground-state intra- molecular properties of the protonated retinal Schiff base are decisive for the proton-pumping activity of BR. In particular, the torsional stability of the 13-14 double bond is found to be of cardinal importance. The barrier for the isomerization around this bond is modified upon substitution of the methyl group at C13 by the residues H, C2H5, CF3, and OCH3. The activation energy for a thermal all-trans-- 13-cis isomerization is increased for the 13- desmethyl compound, is found similar to retinal for the CF3 residue, is slightly smaller for the C2H5 substituent, and is strongly decreased for the 13-methoxy derivative. Depending on the magnitude of the isomerization barrier, BRs proton pump cycle is slowed down, remains unaltered, is accelerated, or is prevented. Our study proves the value of quantumchemical calculations for an understanding of substitution effects and intramolecular chromophore prop- erties on the function of BR. The use of the computer facilities of the Max-Planck-Institut fur Plasma- physik is gratefully acknowledged. This project has been supported by the Deutsche Forschungs Gemeinschaft (SFB-143 C1, A2). Receivedfor publication 31 May 1984 and infinalform 23 August 1984.",
year = "1985",
doi = "10.1016/S0006-3495(85)83925-4",
language = "English (US)",
volume = "47",
pages = "349--355",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "3",
}