Are Protein Cavities and Pockets Commonly Used by Redox Active Signalling Molecules?

Abstract

It has been well known for a long time that inert gases, such as xenon (Xe), have significant biological effects. As these atoms are extremely unlikely to partake in direct chemical reactions with biomolecules such as proteins, lipids, and nucleic acids, there must be some other mode of action to account for the effects reported. It has been shown that the topology of proteins allows for cavities and hydrophobic pockets, and it is via an interaction with such protein structures that inert gases are thought to have their action. Recently, it has been mooted that the relatively inert gas molecular hydrogen (H2) may also have its effects via such a mechanism, influencing protein structures and actions. H2 is thought to also act via interaction with redox active compounds, particularly the hydroxyl radical (·OH) and peroxynitrite (ONOO−), but not nitric oxide (NO·), superoxide anions (O2·−) or hydrogen peroxide (H2O2). However, instead of having a direct interaction with H2, is there any evidence that these redox compounds can also interact with Xe pockets and cavities in proteins, either having an independent effect on proteins or interfering with the action of inert gases? This suggestion will be explored here.