Protein functional group properties, influences

There are at least two ways by which lipids can affect protein structure and function and thereby cell function. Protein function is influenced by specific protein-lipid interactions that depend on the chemical and structural anatomy of lipids (head group, backbone, alkyl chain length, degree of unsaturation, chirality, ionization, and chelating properties). However, protein function is also influenced by the unique self-association properties of lipids that result from the collective properties (fluidity, bilayer thickness, shape, and packing properties) of the lipids organized into membrane structures. 

However, it was immediately recognized by peptide chemists that, even in the cases where a direct (backbone)peptide -protein(backbone) interaction is not operative, the backbone conformation may dramatically influence the biological response. It is evident that the introduction of new, promising peptidomimetics is based primarily on the combined knowledge of the complementary conformational, topochemical, and electronic properties of the native peptide and of its address (in other words, of the receptor or the active site of the enzyme with which it interacts). Then, the design of peptidomimetics as potential bioactive compounds must take into particular account two structural factors (i) a favorable fit (tertiary structure) with respect to the corresponding complementary spatial situation at the active site (ii) the placement of structural elements (e.g., functional groups, polar and... 

The conformation of the peptide chain will affect all hydrodynamic spectral and optical rotatory properties and will influence the chemical behavior of specific functional groups. The relationships between these measurable variables and the actual conformations remain elusive, but changes in the parameters may be used to indicate changes in conformation. Unfortunately, the magnitude of the structural changes to be inferred are not always clear. [See the general review of protein de-naturation by Tanford (333).]... 

The interaction of water with proteins is of paramount importance for maintaining the structure and functional properties of proteins in vivo, but also influences texture and other functional properties of foods. Proteins contain essentially three types of functional groups interacting with water ... 

Typically proteins and especially enzymes contain only a few residues that are absolutely vital for function. In contrast there are usually many other residues of the same type in the protein that do not fulfill any special role. In many cases the catalytic residues have different chemical and physical properties from the same amino acid in solution for example, the pKa of the side chain might be several pH units higher or lower than the free amino acid. It is generally found that the behavior of an amino acid is profoundly influenced by the context of that amino acid within the protein. Altering the chemical properties of a functional group is one of the major attributes of protein structure and appears to be essential for the activity of most enzymes. There are many ways in which this is achieved however, a simple example is placement of a charged residue in the interior of a protein such that the deionized state is favored. This serves to raise the pKa of aspartate and glutamate and lower the pKa of lysine. 

In this review isentropic compressibility data have been compiled for aqueous solutions of the amino acids, including all those found in proteins, of various peptides of low molar mass, and of many proteins. For both the small molecule and protein systems, it is clear that this thermodynamic property is a particularly sensitive measure of hydration effects in aqueous solution. For the small solutes attempts have been made to rationalize the compressibility data in terms of the interactions that occur between the various functional groups and solvent water. For proteins it has been shown that the compressibilities are not correlated with any one structural characteristic. Various characteristics such as amino acid composition, hydrophobicity and the degree of secondary structure all influence, to some degree, the compressibility of a protein. Compressibility measurements on protein solutions also provide an important means to determine the volume fluctuation of a protein. We believe that compressibility measurements on aqueous solutions of these biologically important molecules provide a very powerful means of probing and characterizing solute -water interactions in these systems. 

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