Protein-Assisted Pericyclic Reactions: An Alternate Hypothesis for the Action of Quantal Receptors

Abstract

The rules for allowable pericyclic reactions indicate that the photoisomerizations of retinals in rhodopsins can be formally analogous to thermally promoted Diels-Alder condensations of monoenes with retinols. With little change in the seven-transmembrane helical environment these latter reactions could mimic the retinal isomerization while providing highly sensitive chemical reception. In this way archaic progenitors of G-protein-coupled chemical quantal receptors such as those for pheromones might have been evolutionarily plagiarized from the photon quantal receptor, rhodopsin, or vice versa. We investigated whether the known structure of bacteriorhodopsin exhibited any similarity in its active site with those of the two known antibody catalysts of Diels-Alder reactions and that of the photoactive yellow protein. A remarkable three-dimensional motif of aromatic side chains emerged in all four proteins despite the drastic differences in backbone structure. Molecular orbital calculations supported the possibility of transient pericyclic reactions as part of the isomerization-signal transduction mechanisms in both bacteriorhodopsin and the photoactive yellow protein. It appears that reactions in all four of the proteins investigated may be biological analogs of the organic chemists' chiral auxiliary-aided Diels-Alder reactions. Thus the light receptor and the chemical receptor subfamilies of the heptahelical receptor family may have been unified at one time by underlying pericyclic chemistry.

Influence of Proline on the Thermostability of the Active Site and Membrane Arrangement of Transmembrane Proteins

“…1, b and c). Thus, the retinal molecule and the RBP should be considered the active site of bR, as it should be considered for rhodopsin and other microbial rhodopsins (7)(8)(9)(10)(11). A proof of this comes from directed mutagenesis studies of bR, which have been used to switch the proton pumping function to chloride pumping function (i.e., halo rhodopsin-like protein) (10) or to a sensory receptor protein (i.e., sensory rhodopsin-like protein) (12), mimicking other retinal proteins.…”

Full-Quantum chemical calculation of the absorption maximum of bacteriorhodopsin: a comprehensive analysis of the amino acid residues contributing to the opsin shift

“…8 ). Accordingly, much attention has been paid to the electronic interaction between the chromophore and the triad 13 , 59 . In particular, based on careful calculations using our original QM/MM theory with a polarizable MM region, we showed that these residues undergo a large degree of electronic polarization in response to the excitation of the chromophore and contribute to a red-shift of 0.18 eV (obtained from the data for the WT, W86A, Y185A and W189A models in Table 3 of ref.…”