B/C structures, the origin of R- and â-bands has been
assigned to twists around C12/C13 and C6/C7 bonds,
respectively.8 Although it is generally accepted that the two
positive CEs reflect the interaction between the retinal
chromophore and its protein environment as well as chro-
mophoric twists of polyene chain, the absolute sense of twist
around the 6-s and 12-s bonds, or the absolute conformation
of the 11-cis-retinylidene chromophore in rhodopsin around
these bonds, remained to be established.
We recently investigated the absolute sense of twist around
the 12-s bond based on exciton-coupled CD of 11,12-
dihydrorhodopsin pigments.9 Namely, since this CD method
depends on the through-space coupling of two or more
isolated chromophores,10 the single twisted polyene chain
in native 11-cis-retinal was separated into two independent
conjugated systems by saturation of the central 11-ene. The
triene and diene thus generated interacted through space
within the retinal binding site to give a negative exciton CD
couplet reflecting the negative C12/C13 absolute twist in the
dihydroretinal analogues (Figure 3).
Figure 1. The 11-cis-retinylidene chromophore 1 of rhodopsin is
not planar, that is, planes A, B, and C are not coplanar.
mophore in rhodopsin is central for understanding the
changes in chromophore/receptor interactions along the visual
transduction pathway. In addition, the nonplanar arrangement
of the retinal conformation together with other factors, such
as the distance between the PSB and its counterion and the
electrostatic charge distribution within the retinal binding site,
plays a critical role in regulating the absorption maxima of
visual pigments covering the wide range of wavelengths from
the UV region to around 640 nm.7
Figure 3. Absolute sense of twist around C12/C13 bond of the
retinal chromophore in rhodopsin deduced by negative CD couplets
of 11,12-dihydrorhodopsin pigments.
The nonplanar conformation of the retinal chromophore
also accounts for the unique circular dichroic (CD) spectrum
of rhodopsin. Native rhodopsin exhibits two positive Cotton
effects (CE) in its CD spectrum at 480 nm (∆ꢀ ) +2.8,
R-band) and 337 nm (∆ꢀ ) +9.8, â-band) (Figure 2). On
the basis of the chiroptical data of rhodopsin pigments
incorporating retinal analogues with either coplanar A/B or
This negative helicity of the retinal chromophore agrees
with theoretical calculations by Kakitani et al. and solid-
state NMR studies by Han and Smith.11 However, in a recent
ab initio study,12 the chiroptical data of PSB formed from
methylamine and 11-cis-retinal with four arbitrarily assigned
(7) (a) Nakanishi, K. Am. Zool. 1991, 31, 479. (b) Nakanishi, K. Pure
Appl. Chem. 1991, 63, 161. (c) Yoshizawa, T. Biophys. Chem. 1994, 50,
17.
(8) (a) Fukada, Y.; Shichida, Y.; Yoshizawa, T.; Ito, M.; Kodama, A.;
Tsukida, K. Biochemistry 1984, 23, 5826. (b) Ito, M.; Hiroshima, T.;
Tsukida, K.; Shichida, Y.; Yoshizawa, T. J. Chem. Soc., Chem. Commun.
1985, 1443. (c) Katsuta, Y.; Sakai, M.; Ito, M. J. Chem. Soc., Perkin Trans.
1 1993, 2185. (d) Ito, M.; Katsuta, Y.; Imamoto, Y.; Shichida, Y.;
Yoshizawa, T. Photochem. Photobiol. 1992, 56, 915.
(9) Tan, Q.; Lou, J.; Borhan, B.; Karnaukhova, E.; Berova, N.; Nakanishi,
K. Angew. Chem., Int. Ed. Engl. 1997, 36, 2089.
(10) Nakanishi, K.; Berova, N. In Circular Dichroism: Principles and
Applications; Nakanishi, K., Berova, N., Woody, R. W., Eds.; VCH
Publishers: 1994; pp 361-398.
(11) (a) Kakitani, H.; Kakitani, T.; Yomosa, S. J. Phys. Soc. Jpn. 1977,
42, 996. (b) Han, M.; Smith, S. O. Biochemistry 1995, 34, 1425; 1997, 36,
7280.
(12) Buss, V.; Kolster, K.; Terstegen, F.; Vahrenhorst, R. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 1893.
Figure 2. UV/vis (___, ꢀ) and CD (- - -, ∆ꢀ) spectra of bovine
rhodopsin in 23 mM octyl glucoside buffer solution (pH 7.0).
52
Org. Lett., Vol. 1, No. 1, 1999