Internal Water Molecules as Integral Part of Protein Structures

5 Internal Water Molecules as Integral Part of Protein Structures 

Without water, proteins lose their three-dimensional structure. They denature and their biological functions disappear. Water molecules not only hydrate the surface of proteins and occupy the volume between the protein molecules in crystals, as discussed in Part IV, but they are also found in specific locations within their interior. Since water molecules are so essential, their interactions with main-chain and side-chain atoms of a protein deserve special attention [621, 622]. 

Internal water is an integral part of a protein structure. Even globular proteins of small size are observed to contain buried water molecules. Examples are pancreatic trypsin inhibitor, with 58 amino acid residues and 4 interior water molecules, lysozyme with 129 residues and 4 waters, and larger proteins like ac-tinidin with 218 residues which may contain 10 to 20 molecules of internal water (Fig. 19.13). These water molecules can be buried deep inside the globular proteins or located in cavities near the surface. In some cases, therefore, the distinction in-ternal/external water can be ambiguous. 

Internal water molecules may be located in the same sites in related proteins. In many proteins, internal waters are an essential part of the three-dimensional structure and their positions are typical for a whole family of proteins. Thus, in the three related plant cysteine proteinases, actinidin, papain, and calotropin Dl, 15 of the 16 internal waters (8 of which are illustrated in Fig. 19.13) are found in 

The conservation of internal water structure suggests that the hydrogen-bonding networks involved in their binding are identical or nearly so within the families. This implies that any changes in amino acid sequence (mutations) in the proximity of the water molecules are such that the networks are not affected and are retained during evolution. 

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