Proton transfer in biological systems

Proton transfer (PT) reactions are among the most common reactions in the biosphere, being involved both in light initiated oxygen fixing photosynthetic reactions and in the use of chemical energy in mitochondrial respiration. Although they may show up in very different chemical reactions, these steps are fundamental in as diverse organisms as photosynthetic bacteria, higher plants and mammals.

Many of the proton transfer reactions are either linked to or directly initiated by a primary step in which a photon is absorbed. For reactions that are not light initiated, the judicious use of photo-triggers, e.g. the use of photoacids, has been a powerful tool to access the time course of proton transfer reactions.

The collection of papers in this special issue, far from offering a comprehensive overview of the extensive field of proton transfer reactions in biological systems, aims at giving some insight on selected topics, including fundamental mechanistic aspects and applications for the investigation of biologically relevant processes. Several aspects of the current research on PT reactions are covered by four perspectives and a forum, while seven full length papers offer original research on contemporary topics.

Excited state PT in green fluorescent proteins is a field of active debate where models are continuously challenged by new experimental findings, mostly due to the integrated use of site-directed mutagenesis and novel experimental methods, spanning from single molecule to ultra-fast, time-resolved spectroscopy. In several mutants, proton transfer either in the ground or in the excited state is coupled to a light-dependent photoswitching, which can be probed also at the single molecule level (see papers by Habuchi et al.¹ and van Thor and Sage²).

Several other fundamental processes dealt with by papers appearing in this special issue involve proton transfer steps as light activated proton pumps (Brown and Jung,³ Bondar et al.⁴), photoreceptors (Borucki⁵), and proton channels (Pinto and Lamb⁶). PT reactions are often coupled to other, light activated primary reactions, as in the case of the CO complexes of cytochrome c oxidase (Larsen⁷).The native proton transfer reactions in cytochrome c oxidase are very intricate. The contribution by Popovic and Stuchebrukhov⁸ demonstrates the capabilities of current theoretical approaches by shining light on the role of a critical protonatable residue.

The inherent complexity of proteins and other macromolecular constituents of the cell makes the study of proton migration and exchange generally difficult to model. The presence of a large number of interacting titratable residues on each macromolecule is at the origin of the flexibility and efficiency of the PT reactions. A tremendous source of complexity is the coupling of the dynamics of the macromolecule and the solvent with the interactions between ionisable residues. The influence of the electrical properties of the membrane on proton exchange between the surface and the aqueous bulk phase is addressed in the survey by Mulkidjanian and Cherepanov.⁹

The enormous complexity of the PT process prevents the application of quantitative approaches to the modelling and several drastic simplifications and/or assumptions must be made. The efforts in the modelling include computational methods, with attempts at treating explicitly the dynamics of the protein, solvated ions and the solvent, as discussed by Gutman et al.¹⁰ Approaches at treating the thermodynamic aspects of proton transfer reactions for interacting sites are proposed by Klingen et al.,¹¹ with the derivation of quantitative realistic models.

A new dimension to proton transfer in the study of biological systems is the time- and space-controlled photoinduced release of protons from so called photolabile caged compounds that allow to obtain pH-changes on the nanosecond time scale. Viappiani and coworkers nicely characterize two of those caged compounds with a proton transfer from the uncaged donor to bulk water. An example for the versatility of such a fast pH jump is given with a study of an acid induced unfolding process.¹²

It is our hope that this collection, providing state of the art information, will be a useful reference source for recent developments in the field of proton transfer reactions in biological systems. We also hope that the papers collected in this special issue will foster interest in this interdisciplinary field, where physics, chemistry and biology have to interact.

References

1. S. Habuchi, P. Dedecker, J. Hotta, C. Flors, R. Ando, H. Mizuno, A. Miyawaki and J. Hofkens, Photo-induced protonation/deprotonation in the GFP-like fluorescent protein Dronpa: mechanism responsible for the reversible photoswitching, Photochem. Photobiol. Sci., 2006, 567.
2. J. J. van Thor and J. T. Sage, Charge transfer in green fluorescent protein, Photochem. Photobiol. Sci., 2006, 597.
3. L. S. Brown and K. Jung, Bacteriorhodopsin-like proteins of eubacteria and fungi: the extent of conservation of the haloarchaeal proton-pumping mechanism, Photochem. Photobiol. Sci., 2006, 538.
4. A. Bondar, J. C. Smith and S. Fischer, Structural and energetic determinants of primary proton transfer in bacteriorhodopsin, Photochem. Photobiol. Sci., 2006, 547.
5. B. Borucki, Proton transfer in the photoreceptors phytochrome and photoactive yellow protein, Photochem. Photobiol. Sci., 2006, 553.
6. L. H. Pinto and R. A. Lamb, Influenza virus proton channels, Photochem. Photobiol. Sci., 2006, 629.
7. R. W. Larsen, Time-resolved thermodynamic profiles for CO photolsysis from the mixed valence form of bovine heart cytochrome c oxidase, Photochem. Photobiol. Sci., 2006, 603.
8. D. M. Popovic and A. A. Stuchebrukhov, Two conformational states of Glu242 and pK_as in bovine cytochrome c oxidase, Photochem. Photobiol. Sci., 2006, 611.
9. A. Y. Mulkidjanian and D. A. Cherepanov, Probing biological interfaces by tracing proton passage across them, Photochem. Photobiol. Sci., 2006, 577.
10. M. Gutman, E. Nachliel and R. Friedman, The dynamics of proton transfer between adjacent sites, Photochem. Photobiol. Sci., 2006, 531.
11. A. R. Klingen, E. Bombarda and G. M. Ullmann, Theoretical investigation of the behavior of titratable groups in proteins, Photochem. Photobiol. Sci., 2006, 588.
12. S. Abbruzzetti, S. Sottini, C. Viappiani and J. E. T. Corrie, Acid-induced unfolding of myoglobin triggered by a laser pH jump method, Photochem. Photobiol. Sci., 2006, 621.

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