Formation of an unusual glutamine tautomer in a blue light using flavin photocycle characterizes the light-adapted state

Joshua J. Goings, Pengfei Li, Qiwen Zhu, Sharon Hammes-Schiffer

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Blue light using flavin (BLUF) photoreceptor proteins are critical for many light-activated biological processes and are promising candidates for optogenetics because of their modular nature and long-range signaling capabilities. Although the photocycle of the Slr1694 BLUF domain has been characterized experimentally, the identity of the light-adapted state following photoexcitation of the bound flavin remains elusive. Herein hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations of this photocycle provide a nonequilibrium dynamical picture of a possible mechanism for the formation of the light-adapted state. Photoexcitation of the flavin induces a forward proton-coupled electron transfer (PCET) process that leads to the formation of an imidic acid tautomer of Gln50. The calculations herein show that the subsequent rotation of Gln50 allows a reverse PCET process that retains this tautomeric form. In the resulting purported light-adapted state, the glutamine tautomer forms a hydrogen bond with the flavin carbonyl group. Additional ensemble-averaged QM/MM calculations of the dark-adapted and purported light-adapted states demonstrate that the light-adapted state with the imidic acid glutamine tautomer reproduces the experimentally observed spectroscopic signatures. Specifically, the calculations reproduce the red shifts in the flavin electronic absorption and carbonyl stretch infrared spectra in the light-adapted state. Further hydrogen-bonding analyses suggest the formation of hydrogen-bonding interactions between the flavin and Arg65 in the light-adapted state, providing a plausible explanation for the experimental observation of faster photoinduced PCET in this state. These characteristics of the light-adapted state may also be essential for the long-range signaling capabilities of this photoreceptor protein.

Original languageEnglish (US)
Pages (from-to)26626-26632
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - Oct 27 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


  • Molecular dynamics
  • Photoreceptor
  • Proton-coupled electron transfer
  • Time-dependent density functional theory


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