Use of noble gases xenon and krypton as heavy atoms in protein structure determination.

Publisher Summary This chapter presents various aspects of the preparation of xenon and krypton derivatives and their use as heavy atoms or anomalous scatterers in protein crystallography. The noble gas atoms are able to diffuse rapidly toward potential interaction sites in proteins via the solvent channels that are always present in crystals of macromolecules. Xenon and krypton derivatives of proteins can be obtained by subjecting a native protein crystal to a xenon or krypton gas atmosphere pressurized in the range of 1–100 bar. The number and occupancies of xenon/krypton-binding sites vary with the applied pressure. The interaction of noble gas atoms with proteins is the result of noncovalent weak-energy van der Waals forces, and therefore the process of xenon/krypton binding is completely reversible. With proteins, however, the interactions of xenon and krypton are of noncovalent origin and are therefore similar in nature to the forces that give rise to the formation of other well-known complexes of xenon and krypton with small molecules. The key physical parameter in xenon/krypton–protein interactions is the electronic polarizability of the noble gas atoms. The usual repulsive forces between atoms and molecules that are in close contact with each other also play an important role because they determine the minimum size that a cavity must have for xenon or krypton to bind into it. With the current emphasis on high-throughput macromolecular crystallography, the use of xenon and krypton derivatives should feature prominently in the list of available tools to solve protein structures.