Catalysis of Ground State cis\(\rightarrow\) trans Isomerization of Bacteriorhodopsin’s Retinal Chromophore by a Hydrogen-Bond Network

Abstract

For the photocycle of the membrane protein bacteriorhodopsin to proceed efficiently, the thermal 13-cis to all-trans back-isomerization of the retinal chromophore must return the protein to its resting state on a time-scale of milliseconds. Here, we report on quantum mechanical/molecular mechanical energy calculations examining the structural and energetic determinants of the retinal cistrans isomerization in the protein environment. The results suggest that a hydrogen-bonded network consisting of the retinal Schiff base, active site amino acid residues, and water molecules can stabilize the twisted retinal, thus reducing the intrinsic energy cost of the cistrans thermal isomerization barrier.

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Acknowledgements

N. E.-M. and J. C. S. were supported by a grant from the Deutsche Forschungsgemeinschaft (DFG), SM 63/7-3. P. P. and M. E. were supported by a grant from the Deutsche Forschungsgemeinschaft (DFG), EL 206/8-1.

Funding

This study was funded by Grants SM 63/7-3 and EL 206/8-1 from the Deutsche Forschungsgemeinschaft. N. E.-M. gratefully acknowledges financial support in part from the Volkswagen Stiftung (grant number 86 539). A.N. B acknowledges financial support in part from the DFG Collaborative Research Center SFB1078’ Protonation Dynamics in Protein Function’ (Project C4) and from the Freie Universitt Berlin within the Excellence Initiative of the German Research Foundation.

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Correspondence to Nadia Elghobashi-Meinhardt.

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Elghobashi-Meinhardt, N., Phatak, P., Bondar, A. et al. Catalysis of Ground State cis\(\rightarrow\) trans Isomerization of Bacteriorhodopsin’s Retinal Chromophore by a Hydrogen-Bond Network. J Membrane Biol 251, 315–327 (2018). https://doi.org/10.1007/s00232-018-0027-x

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Keywords

  • Bacteriorhodopsin
  • Retinal
  • Isomerization
  • QM/MM
  • Energy
  • Calculations