Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins.
Comparative modeling and ab initio multiconfigurational quantum chemistry are combined to investigate the reactivity of the human nonvisual photoreceptor melanopsin. It is found that both the thermal and photochemical isomerization of the melanopsin 11-cis retinal chromophore occur via a space-saving mechanism involving the unidirectional, counterclockwise twisting of the =C11H-C12H= moiety with respect to its Lys340-linked frame as proposed by Warshel for visual pigments [Warshel A (1976) Nature 260(5553):679-683]. A comparison with the mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual photoreceptors shows that such a mechanism is not affected by the diversity of the three chromophore cavities. Despite such invariance, trajectory computations indicate that although all receptors display less than 100 fs excited state dynamics, human melanopsin decays from the excited state ∼40 fs earlier than bovine rhodopsin. Some diversity is also found in the energy barriers controlling thermal isomerization. Human melanopsin features the highest computed barrier which appears to be ∼2.5 kcal mol(-1) higher than that of bovine rhodopsin. When assuming the validity of both the reaction speed/quantum yield correlation discussed by Warshel, Mathies and coworkers [Weiss RM, Warshel A (1979) J Am Chem Soc 101:6131-6133; Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) Science 254(5030):412-415] and of a relationship between thermal isomerization rate and thermal activation of the photocycle, melanopsin turns out to be a highly sensitive pigment consistent with the low number of melanopsin-containing cells found in the retina and with the extraretina location of melanopsin in nonmammalian vertebrates.
Dipartimento di Biotecnologie, Chimica e Farmacia, Università di Siena, I-53100 Siena, Italy.
Silvia
S
Rinaldi
Federico
F
Melaccio
Samer
S
Gozem
Francesca
F
Fanelli
Massimo
M
Olivucci
D000042:Absorption; D000818:Animals; D002417:Cattle; D049832:Decapodiformes / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007536:Isomerism; D008027:Light; D008958:Models, Molecular; D008968:Molecular Conformation; D055668:Photochemical Processes; D011687:Purines / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D017299:Rod Opsins / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D000099210:Melanopsin
D007093:Imidazoles; D011687:Purines; D012243:Rhodopsin; D017299:Rod Opsins; D000099210:Melanopsin; C438613:8-ethyl-4-methyl-2-phenyl-4,5,7,8-tetrahydro-1H-imidazo(2,1-i)purin-5-one
QM/MM method; computational photobiology; conical intersection; thermal noise in photoreceptors; ultrafast isomerization