Amino acid side chains hydrophilic

Fig. 1. The side chain R of the 20 standard amino acids +H3N—CHR—COO at pH 7. For proline, the complete stmcture is shown. Amino acid side chains can be categorized as aUphatic (Gly, Ala, Val, Leu, and He), hydrophilic (Ser, Thr, Asp, Glu, Asn, Gin, Lys, and Arg), sulfur-containing (Cys and...

We encountered the properties of hydrophilic and hydrophobic molecules in our thoughts about driving forces for formation of three-dimensional protein structures. Specifically, proteins fold in a way that puts most of the hydrophobic amino acid side chains into the molecular interior, where they can enjoy each other s company and avoid the dreaded aqueous environment. At the same time, they fold to get the hydrophilic amino acid side chains onto the molecular surface, where they happily interact with that enviromnent. The same ideas are important for the double-stranded helical structure of DNA. The hydrophobic bases are localized within the double hehx, where they interact with each other, and the strongly hydrophilic sugar and phosphate groups are exposed on the exterior of the double helix to the water environment. Now, we need to understand something more about structural features that control these properties. 

This chapter aims to summarize our efforts to investigate the effects of fluorinated amino acid substitutes on the interactions with natural protein environments. In addition to a rather specific example concerning the interactions of small peptides with a proteolytic enzyme, we present a simple polypeptide model that aids for a systematic investigation of the interaction pattern of amino acids that differ in side chain length as well as fluorine content within both a hydrophobic and hydrophilic protein environment. Amino acid side chain fluoiination highly affects polypeptide folding due to steric effects, polarization, and fluorous interactions. 

The a-helical coiled coil-based screening system already provided a wide variety of information about the interactions of fluorinated amino acids within hydrophobic and hydrophilic protein environments. Investigations on the thermal stability as well as the replicase activity have both emphasized the orthogonal properties of fluorinated aliphatic amino acid side chains. The term orthogonal in this context has been chosen by us to demonstrate that they are in fact hydrophobic... 

Apolipoproteins ( apo designates the protein in its lipid-free form) combine with lipids to form several classes of lipoprotein particles, spherical complexes with hydrophobic lipids in the core and hydrophilic amino acid side chains at the surface (Fig. 21-39a). Different combinations of lipids and proteins produce particles of different densities, ranging from chylomicrons to high-density lipoproteins. These particles can be separated by ultracentrifugation (Table 21-2) and visualized by electron microscopy (Fig. 21-39b). 

A graphic representation of a three-dimensional model of the protein, cytochrome c. Amino acids with nonpolar, hydrophobic side chains (color) are found in the interior of the molecule, where they interact with one another. Polar, hydrophilic amino acid side chains (gray) are on the exterior of the molecule, where they interact with the polar aqueous solvent. (Illustration copyright by Irving Geis. Reprinted by permission.)... 

For proteins with multiple transmembrane domains, it is not necessary to have exclusively hydrophobic amino acids a pair of amino acids with opposite charges may be present in the lipophilic environment of the membrane. Therefore a search for amphipathic a-helices must be undertaken. Amphipathic helices have well-defined hydrophobic character, the hydrophobic face which would project towards the membrane/lipid environment, and a hydrophilic face, which would project out into the aqueous phase or towards the core of a helix bundle. Often times the distinction is not clear and there are regions of mixed hydrophobic/hydrophilic character. Graphically this can be realized with a helical-wheel representation in which the amino acid side chains project out, at 100 degree intervals, from the view along the long, helical axis. 

In an attempt to find out more about the nature of the secondary binding site in penicillopepsin. Mains et al. (76) analysed the nature of the amino acid side chains at positions removed from the sensitive peptide bond. An abbreviated summary of the results is given in Table VII. The number of hydrophobic and hydrophilic side chains respectively are listed for four amino acids on either side of every peptide bond broken in the B-chain of insulin and in glucagon. The positions are numbered Pi, P2, P/, P2 etc. as defined by Berger and Schechter (103). The choice of four positions was taken from the Frutons work (73) on the specificity of pepsin and the eflFect of chain length on catalytic efficiency. The largest eflFects were observed with substrates having three to four... 

Several scales presented in Table 3 show promise as measures of fundamental electronic properties of amino acids as does the Hp index of hydrophilicity. Nevertheless, additional improvements are desirable. The polarizability index of steric effects should include hyperconjugation as a component. Clearly, the movement of electrons into antibonding orbitals contributes to molecular deformation (24). The Hp index is based on PM3 calculations of electron densities for the component atoms of amino acid side chains. A more integrative approach with higher-order theory is likely to refine this measure additionally. 

By inserting appropriate amino acid side chains (e.g., hydrophilic and hydrophobic), it is feasible to construct amphiphilic helices (with two faces that possess different properties). The conformational strategy should take into account the parameters typical of each of the two helices, in particular that 1) The a-helix (Fig. la) is characterized by a fractional number of amino acids per turn (=3.5) and consequently its smallest repeat (i.e., the shortest main-chain length that brings two side chains exactly one on top of the other) is a heptad (7 residues) and 2) in the 3io-helix (Fig. lb), which has an integer number of amino acids per turn (=3.0), a triplet of residues selected carefully will produce the expected amphiphiUcity. 

Two important features emerge from our examination of these three examples of membrane protein structure. First, the parts of the protein that interact with the hydrophobic parts of the membrane are coated with nonpolar amino acid side chains, whereas those parts that interact with the aqueous environment are much more hydrophilic. Second, the structures positioned within the membrane are quite regular and, in particular, all backbone hydrogen-bond donors and acceptors participate in hydrogen bonds. Breaking a hydrogen bond within a membrane is quite unfavorable, because little or no water is present to compete for the polar groups. 

The membrane proteins may be transmembrane, splitting the lipid billayer Fig. (10). In this case the protein length is about lOnm and has hydrophilic and hydrophobic regions. The polar amino acid side chains are exposed to aqueous environment and can... 

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