The organization and function of water in protein crystals

Abstract

Dry proteins are dead, or at best asleep. Substitution of D2O can drastically alter biological activity. Water is thus essential in maintaining the structural integrity of biologically active macromolecules, and is implicated in their functioning. Such water may occupy a range of dynamical states, from being strongly bound and localized, to more labile and 'liquid-like'. Spatially ordering the macromolecules aids the search for the more localized water molecules. For example, diffraction experiments on singly crystals can resolve 'bound' water molecules within a protein molecule--ofter at active sites, coordinated to metals or ions. Less precise information is obtained on the partially occupied external water sites, which are of importance to the folding and dynamics of the biomolecule. Orientation of fibrous molecules increases the information obtainable from n.m.r. experiments. Combination of other experimental results on disordered aggregates (e.g. in solution) with chemical and structural data on the macromolecule and water itself yields useful, if circumstantial, information. Statistical and computer techniques may help to elucidate the complex nature of water-protein interactions, and to interpret the results of more complex experiments.

The interplay of electrostatic fields and binding interactions determining catalytic-site reactivity in actinidin. A possible origin of differences in the behaviour of actinidin and papain

“…The charge on the two buried carboxylate side chains of Glu-35 and Glu-50 should be partly neutralized by Lys-17 and additionally by Lys-181, which may interact with Glu-35 through two water molecules, which may have a charge spreading role as discussed by Finney (1977). The other buried carboxy group (Glu-52) is in a partly hydrophobic environment adjacent to Ile-83, and Phe-76 and has no obvious cationic partner.…”

Structural insights from water-ferredoxin interaction in mesophilic algae and halophilic archaea

“…In general, the protein structure maintains layers of hydration shells [4]. Upon crystallization, although bulk waters are largely eliminated, shell-waters (SWs) remain bound to protein [5]. As these SWs are interacting with different a] atom-types and b] segments of secondary structure and c] regions such as core, surface, and cavity of 3D-structure of protein [5,6], detailed understanding of these interactions may illuminate the role of SWs for the maintenance of the structure, stability, recognition, and function of proteins.…”

“…While SWs in the core and cavities are directly related to the stability and function, surface-bound-waters are related to the binding specificity of protein. Notably, in the core of the protein, destabilizing isolated charged-atoms, hydrogen-bond donor or acceptor groups and flexible arrangements of secondary structure are largely satisfied by SWs and thereby contribute to the overall stability of protein [5,6]. Internal cavities could be filled by ordered or disordered SWs.…”

Internal water bridge and antiparallel sheet in the structure of benzyloxycarbonyl-L-alanyl-D-phenylalanyl-L-proline monohydrate

“…Bound water molecules are believed to play an important role in maintaining the structural integrity of proteins, probably by contributing to the local stabilization of conformation (Finney, 1977). It has been noticed in protein structures that more water molecules bind to the main chain than to side chains.…”

“…It has been noticed in protein structures that more water molecules bind to the main chain than to side chains. Although the main chain has an equal number of CO and NH groups, more water molecules are known to bind to the former than to the latter in proteins (Finney, 1977) as well as in small peptides (Yang et al, 1979).…”