Nonpolar amino acids

Hydrogen bonding stabilizes some protein molecules in helical forms, and disulfide cross-links stabilize some protein molecules in globular forms. We shall consider helical structures in Sec. 1.11 and shall learn more about ellipsoidal globular proteins in the chapters concerned with the solution properties of polymers, especially Chap. 9. Both secondary and tertiary levels of structure are also influenced by the distribution of polar and nonpolar amino acid molecules relative to the aqueous environment of the protein molecules. Nonpolar amino acids are designated in Table 1.3. 

The nonpolar amino acids (Figure 4.3a) include all those with alkyl chain R groups (alanine, valine, leucine, and isoleucine), as well as proline (with its unusual cyclic structure), methionine (one of the two sulfur-containing amino acids), and two aromatic amino acids, phenylalanine and tryptophan. Tryptophan is sometimes considered a borderline member of this group because it can interact favorably with water via the N-H moiety of the indole ring. Proline, strictly speaking, is not an amino acid but rather an a-imino acid. 

Although the side chains of most nonpolar amino acids in soluble proteins are usually buried in the interior of the protein away from contact with the aqueous solvent, a portion of them is exposed at the protein s surface, giving... 

Xiong, H., Bnckwalter, B., Shieh, H.-M., and Hecht, M. H., 1995. Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides. Proceedings of the National Academy of Sciences 92 6349—6353. 

The characteristic coiled-coil motifs found in proteins share an (abcdefg) heptad repeat of polar and nonpolar amino acid residues (Fig. 1). In this motif, positions a, d, e, and g are responsible for directing the dimer interface, whereas positions b, c, and f are exposed on the surfaces of coiled-coil assemblies. Positions a and d are usually occupied by hydrophobic residues responsible for interhelical hydrophobic interactions. Tailoring positions a, d, e, and g facilitates responsiveness to environmental conditions. Two or more a-helix peptides can self-assemble with one another and exclude hydrophobic regions from the aqueous environment [74]. Seven-helix coiled-coil geometries have also been demonstrated [75]. 

Valine (possibly other nonpolar amino acids) Surface tension increase To hydrophobic regions Weak stabilization... 

Membrane integral proteins have transmembrane domains that insert directly into lipid bilayers. Transmembrane domains (TMDs) consist predominantly of nonpolar amino acid residues and may traverse the bilayer once or several times. High-resolution structural information is available for only a few integral membrane proteins, primarily because it is difficult to obtain membrane protein crystals that are adequate for X-ray diffraction measurements. 

Turning to l-AAO, Pantaleone s industrial research group have reported" on the properties and use of an l-AAO from Proteus myxofaciens, overexpressed in Escherichia coli This l-AAO, unusually, appears not to produce H2O2 in the catalytic reaction, thus making the addition of catalase unnecessary. The enzyme has a broad specificity, with a preference for nonpolar amino acids. This l-AAO was used in conjunction with a D-amino acid transaminase (d-AAT) and an alanine racemase (AR) to allow an efficient conversion of L-amino acid in to D-amino acid (Scheme 4). 

The Bristol group of Christine Willis, in collaboration with Amersham International, developed a procedure for deuterium (or labeling of nonpolar amino acids." In the chemical steps, a selectively methyl-labeled oxazolidinone is converted first into a 2-methyl carboxylic acid and then lengthened by two carbon atoms without racemization to yield an a-keto methyl ester (Scheme 9). 

Leucine (Leu or L) ((A)-2-amino-4-methyl-pentanoic acid) is a neutral, aliphatic amino acid with the formula HOOCCH(NH2)CH2CH(CH3)2 and with a hydrocarbon side chain. Leu is classified as a hydrophobic (nonpolar) amino acid. ... 

The ability of both suppressor tRNAs to incorporate the nonpolar amino acid valine as well as the polar noncoded homoglutamate into two proteins was tested in E. coli cell-free transcription-translation systems [35]. The proteins T4... 

Alanine is the simplest nonpolar amino acid. It is derived from glycine by affixing a methyl group to the a carbon atom. 

We are now in a position to nnderstand the molecnlar nature of sickle cell anemia. We need to remember that amino acids come in three flavors nonpolar, charged (highly hydrophilic polar), and uncharged polar. We also need to remember that proteins are organized in a way that hides most of the nonpolar amino acid residues in the molecular interior and exposes most of the charged, in particular, and uncharged polar residues on the molecnlar snrface. 

Now we can ask what is likely to happen to the three-dimensional structure of a protein if we make a conservative replacement of one amino acid for another in the primary structnre. A conservative replacement involves, for example, substitution of one nonpolar amino acid for another, or replacement of one charged amino acid for another. Intnitively, one would expect that conservative replacements would have rather little effect on three-dimensional protein structure. If an isoleucine is replaced by a valine or leucine, the structnral modification is modest. The side chains of all of these amino acids are hydrophobic and will be content to sit in the molecnlar interior. This expectation is borne out in practice. We have noted earlier that there are many different molecnles of cytochrome c in nature, all of which serve the same basic function and all of which have similar three-dimensional structnres. We have also noted the species specificity of insulins among mammalian species. Here too we find a number of conservative changes in the primary structure of the hormone. Although there are exceptions, as a general rule conservative changes in the primary structnre of proteins are consistent with maintenance of the three-dimensional structures of proteins and the associated biological functions. 

The side chains of nonpolar amino acids are normally clustered in the interior of proteins to shield them from water. 

FIGURE 11-3 Fluid mosaic model for membrane structure. The fatty acyl chains in the interior of the membrane form a fluid, hydrophobic region. Integral proteins float in this sea of lipid, held by hydrophobic interactions with their nonpolar amino acid side chains. Both proteins and lipids are free to move laterally in the plane of the... 

Peripheral proteins are loosely associated with the membrane through electrostatic interactions and hydrogen bonds or by covalently attached lipid anchors. Integral proteins associate firmly with membranes by hydrophobic interactions between the lipid bilayer and their nonpolar amino acid side chains, which are oriented toward the outside of the protein molecule. 

Location of nonpolar amino acids in proteins In proteins found in aqueous solutions, the side chains of the nonpolar amino acids tend to cluster together in the interior of the protein (Figure 1.4). This phenomenon is the result of the hydrophobicity of the nonpolar... 

Classification of the twenty amino acids found in proteins, according to the charge and polarity of their side chains is shown here and continues in Figure 1.3. Each amino acid is shown in its fully protonated form, with dissociable hydrogen ions represented in red print. The pK values for the a-carboxyl and a-amino groups of the nonpolar amino acids are similar to those shown for glycine. (Continued on Figure 1.3.)... 

Nonpolar amino acids (O) cluster on the surface of membrane proteins. 

Location of nonpolar amino acids in soluble and membrane proteins. 

Location of polar and nonpolar amino acid residues The interior of the myoglobin molecule is composed almost entirely of nonpolar amino acids. They are packed closely together, forming a structure stabilized by hydrophobic interactions between these clustered residues (see p. 19). In contrast, charged amino acids are located almost exclusively on the surface of the molecule, where they can form hydrogen bonds, with each other and with water. 

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