Water mediated interaction

Structural studies of a repressor-DNA complex have shown that helices 4 and 5 form a helix-turn-helix motif and that side chains from the recognition helix 5 form water-mediated interactions with bases in the major groove. 

Instead, the Lys side chains bond to Y position carbonyl groups of an adjacent chain, while one Glu directly interacts with a Hyp hydroxyl group. There was also a range of water-mediated interactions involving the polar side chains. In peptide T3-785, with the central region Gly-Ile-Thr-Gly-Ala-Arg-Gly-Leu-Ala, the Arg side... 

Figure 18 Molecular structure of IBP collagen (PDB accession number 1Q7D) showing a direct intrahelical ion bridge and a water-mediated interaction between Glu and Arg of different chains. The figure was generated using the UCSF Chimera package.

Contacts with the catalytic residues, in combination with hydrophobic interactions, are also observed in the complex of an insect a-amylase with the Ragi bifunctional a-amylase/trypsin inhibitor (RBI) [174]. Conversely, the mechanism of inhibition of barley a-amylase by the barley a-amylase/subtilisin inhibitor (BASI) did not involve direct contact between inhibitor residues and the catalytic site [175]. The inhibitor sterically blocks the catalytic site, but does not extend into it. A cavity is created, which is occupied by a calcium ion coordinated by water-mediated interactions with the catalytic residues. 

The bases are numbered outward from the central C and G.) The small solid spheres are water molecules. Notice the water mediated interactions of the basic arginine and lysine side chains with the nucleic acid bases and also the interaction of R240 and R243 (in B) with a backbone phosphate. The overall structure of the protein is similar to that of another leucine zipper shown in Fig. 2-21. From Keller et al.419 Drawings courtesy of Timothy J. Richmond. 

Most of the water-mediated interactions between surfaces are described in terms of the DLVO theory [1,2]. When a surface is immersed in water containing an electrolyte, a cloud of ions can be formed around it, and if two such surfaces approach each other, the overlap of the ionic clouds generates repulsive interactions. In the traditional Poisson-Boltzmann approach, the ions are assumed to obey Boltzmannian distributions in a mean field potential. In spite of these rather drastic approximations, the Poisson-Boltzmann theory of the double layer interaction, coupled with the van der Waals attractions (the DLVO theory), could explain in most cases, at least qualitatively, and often quantitatively, the colloidal interactions [1,2]. 

Fig. 10. Detailed TRAF2-TRADD interaction. (A) Interaction surfaces and their locations on the individual structures (in red). (B) Molecular interactions at the two regions of the interactions. (C, D, E) Details of region I, region II and water-mediated interactions, respectively. (See Color Insert.)...

The water-mediated interactions may also be of considerable importance. In the activated form the lid occupies a new position on the surface of the molecule, some 8 A away from the original location. This deep surface depression extends 10 A into the molecule and is filled in the native enzyme by 18 water molecules, half of which are direcdy hydrogen bonded to the polar protein groups. During the conformational change ail but three of these solvent molecules are expelled. In the lipase-inhibitor complex these three molecules become buried and mediate the polar contacts formed primarily by Asn-87. 

It is well known that water-mediated interaction stabilizes structure of biomolecules [1, 138, 247-250]. Therefore, several model molecular systems have been chosen to probe the water-mediated interactions in biomolecules and a large amount of experimental and theoretical work has been published over the years on this subject [78, 138, 251-258]. Since phenol is the simplest aromatic alcohol resembling chromophore of an aromatic amino acid, hydration of phenol molecules has been studied to understand H-bonding and solute-solvent interaction in biological systems. Several experimental and theoretical calculations have been made on the phenol-water clusters [259-273]. Recently, we have made a comprehensive analysis on structure, stability, and H-bonding interaction in phenol (P1-4), water (W1-4), and phenol-water (PmW (w = 1-3, n = 1-3, w + n < 4)) clusters using ab initio and DFT methods [245]. In this section, electronic structure calculations combined with AIM analysis on phenol-water clusters are presented. 

The role of water in the conformation, the activity and the stability of proteins has been investigated with many experimental and theoretical approaches. Because of its importance it has been coined as the 21 amino acid . There is now sufficient experimental evidence for the fact that dry proteins do not unfold by increased temperature or pressure [21]. Low levels of hydration give rise to a glassy state and the temperature of the glass transition depends on the amount of water as observed for synthetic polymers. Water can therefore be considered as a plasticizer of the protein conformation. Whereas hydrophobic interactions have dominated the interpretation of the data, hydrogen bond networks of water may also play a predominant role in water-mediated interactions [48,49]. 

As we discussed earlier, hydrophobicity is considered at two levels. First is the hydration of a single non-polar solute and the second is pair hydrophobicity, where a water-mediated interaction between two non-polar solutes is articulated. The former is often referred to as hydrophobic hydration. 

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