Amino acids tertiary structure

In addition to the primary structure, proteins also exhibit secondary, tertiary, and quaternary structure. The overall structure of proteins is related to several factors. Primary among these factors is the electrostatic nature of amino acids. The structures displayed in Figure 16.10 do not show the charge distribution displayed by amino acids. In neutral solutions, the carboxyl group tends to donate a proton (hydrogen ion) to the amino group. The transfer of a proton means the amino end of the molecule... 

A prerequisite for the catalytic function of an enzyme is its native tertiary structure which is determined by the number and sequence of amino acids (primary structure) forming the molecule. Favoured by hydrogen bonds, parts of the polypeptide chain exist in an a-helical or a (3-sheet structure (secondary structure). Most enzymes are globular proteins, the tertiary structure of which may be fixed by disulfide bonds between cysteine residues. A famous example is lysozyme (Fig. 20), consisting of 129 amino acids. A defined three-dimensional structure is... 

We have seen that the forces that maintain the secondary structure of a protein are hydrogen bonds between the amide hydrogen and the carbonyl oxygen of the peptide bond. What are the forces that maintain the tertiary structure of a protein The globular tertiary structure forms spontaneously and is maintained as a result of interactions among the side chains, the R groups, of the amino acids. The structure is maintained by the following molecular interactions ... 

Figure 15.22 The structural hierarchy of proteins. A typical protein s structure can be viewed at different levels. Primary structure (shown as a long string of balls leaving and returning to the picture frame) is the sequence of amino acids. Secondary structure consists of highly ordered regions that occur as an a-helix or a p-sheet. Tertiary structure combines these ordered regions with more random sections. In many proteins, several tertiary units interact to give the quaternary structure.

In other words, the sum of functional properties depends on the physicochemical characteristics of the whole system containing the working protein. The determinant properties of the protein itself are the amino acid composition, structure (primary, secondary, tertiary, quaternary), and conformational stability the charge of the molecule and its dimensions, shape, and topography the extent of polarity and hydrophobicity, and the nature of protein-protein interactions. 

Primary structure is the order of the amino acids. Secondary structure is characterized by a repetitive organization of the peptide backbone. Tertiary structure refers to the complete three-dimensional structure of the protein. Quaternary structure describes a protein that has multiple polypeptide chains. 

Peptides are formed by the condensation of carboxyl and amino groups in amino acids. Their primary structure is the sequence of amino acids. Secondary structure is determined by the required planarity of the amide group and interactions between side chains. a-Helices and p-pleated sheets are common motifs. Tertiary structure is the full three-dimensional structure of the peptide. 

Backbone generation is the first step in building a three-dimensional model of the protein. First, it is necessary to find structurally conserved regions (SCR) in the backbone. Next, place them in space with an orientation and conformation best matching those of the template. Single amino acid exchanges are assumed not to affect the tertiary structure. This often results in having sections of the model compound that are unconnected. 

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. 

Figure 1.1 The amino acid sequence of a protein s polypeptide chain is called Its primary structure. Different regions of the sequence form local regular secondary structures, such as alpha (a) helices or beta (P) strands. The tertiary structure is formed by packing such structural elements into one or several compact globular units called domains. The final protein may contain several polypeptide chains arranged in a quaternary structure. By formation of such tertiary and quaternary structure amino acids far apart In the sequence are brought close together in three dimensions to form a functional region, an active site.

Several motifs usually combine to form compact globular structures, which are called domains. In this book we will use the term tertiary structure as a common term both for the way motifs are arranged into domain structures and for the way a single polypeptide chain folds into one or several domains. In all cases examined so far it has been found that if there is significant amino acid sequence homology in two domains in different proteins, these domains have similar tertiary structures. 

What can be done by predictive methods if the sequence search fails to reveal any homology with a protein of known tertiary structure Is it possible to model a tertiary structure from the amino acid sequence alone There are no methods available today to do this and obtain a model detailed enough to be of any use, for example, in drug design and protein engineering. This is, however, a very active area of research and quite promising results are being obtained in some cases it is possible to predict correctly the type of protein, a, p, or a/p, and even to derive approximations to the correct fold. 

Role of the Amino Acid Sequence in Protein Structure Secondary Structure in Protein.s Protein Folding and Tertiary Structure Subunit Interaction.s and Quaternary Structure... 

The secondary and tertiary structures of myoglobin and ribonuclease A illustrate the importance of packing in tertiary structures. Secondary structures pack closely to one another and also intercalate with (insert between) extended polypeptide chains. If the sum of the van der Waals volumes of a protein s constituent amino acids is divided by the volume occupied by the protein, packing densities of 0.72 to 0.77 are typically obtained. This means that, even with close packing, approximately 25% of the total volume of a protein is not occupied by protein atoms. Nearly all of this space is in the form of very small cavities. Cavities the size of water molecules or larger do occasionally occur, but they make up only a small fraction of the total protein volume. It is likely that such cavities provide flexibility for proteins and facilitate conformation changes and a wide range of protein dynamics (discussed later). 

Implicit in the presumption of folding pathways is the existence of intermediate, partially folded conformational states. The notion of intermediate states on the pathway to a tertiary structure raises the possibility that segments of a protein might independently adopt local and well-defined secondary structures (a-helices and /3-sheets). The tendency of a peptide segment to prefer a particular secondary structure depends in turn on its amino acid composition and sequence. 

Two polypeptides, A and B, have similar tertiary structures, but A normally exists as a monomer, whereas B exists as a tetramer, B4. What differences might be expected in the amino acid composition of A versus B ... 

What about tertiary structure Why does any protein adopt the shape it does The forces that determine the tertiary structure of a protein are the same forces that act on ail molecules, regardless of size, to provide maximum stability. Particularly important are the hydrophilic (water-loving Section 2.13) interactions of the polar side chains on acidic or basic amino acids. Those acidic or basic amino acids with charged side chains tend to congregate on the exterior of the protein, where they can be solvated by water. Those amino acids with neutral, nonpolar side chains tend to congregate on the hydrocarbon-like interior of a protein molecule, away from the aqueous medium. 

Proteins have four levels of structure. Primary structure describes a protein s amino acid sequence secondary structure describes how segments of the protein chain orient into regular patterns—either a-helix or /3-pleated sheet tertiary structure describes how the entire protein molecule coils into an overall three-dimensional shape and quaternary structure describes how individual protein molecules aggregate into larger structures. 

FIGURE 1.4 Increasing levels of protein structure. A protein has a given amino acid sequence to make peptide chains. These adopt a 3D structure according to the free energy of the system. Receptor function can change with changes in tertiary or quaternary structure. 

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