title: Steric Effects Govern the Photoactivation of Phytochromes.
abstract: Phytochromes constitute a superfamily of photoreceptor proteins existing in two forms that absorb red (Pr) and far-red (Pfr) light. Although it is well-known that the conversion of Pr into Pfr (the biologically active form) is triggered by a Z→E photoisomerization of the linear tetrapyrrole chromophore, direct evidence is scarce as to why this reaction always occurs at the methine bridge between pyrrole rings C and D. Here, we present hybrid quantum mechanics/molecular mechanics calculations based on a high-resolution Pr crystal structure of Deinococcus radiodurans bacteriophytochrome to investigate the competition between all possible photoisomerizations at the three different (AB, BC and CD) methine bridges. The results demonstrate that steric interactions with the protein are a key discriminator between the different reaction channels. In particular, it is found that such interactions render photoisomerizations at the AB and BC bridges much less probable than photoisomerization at the CD bridge.
authors.affiliation: Division of Theoretical Chemistry, IFM, Linköping University, 581 83, Linköping, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Falklöf
authors.affiliation: Division of Theoretical Chemistry, IFM, Linköping University, 581 83, Linköping, Sweden. bodur@ifm.liu.se.
authors.forename: Bo
authors.identifier: http://orcid.org/0000-0001-5847-1196
authors.initials: B
authors.lastname: Durbeej
mesh_terms: D034301:Deinococcus; D007536:Isomerism; D008956:Models, Chemical; D015394:Molecular Structure; D010834:Phytochrome / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D010834:Phytochrome
keywords: QM/MM modeling; chromophores; isomerization; photoreceptor proteins; range-separated functionals