Unicellular Organisms

Proteins and Enzymes

Primary Structure - It is the linear sequence of the amino acids joined by peptide bonds (the C-N in the ... -N-C-C-{N-C-C-N}- ... backbone). It is the first C there linking to a side chain (R group) that determines the characteristics of the protein. Any number of the 20 different amino acids can be joined in any sequence (only a certain sequences are useful to the organisms). Any given protein has a specific sequence of amino acids. Protein biosynthesis is most commonly performed by ribosomes in cells. Peptides

	can also be synthesised in the laboratory. Since there are about 20,000 genes in human genome but about 100,000 transcripts of protiens, obviously one gene can produce multiple forms. As shown in the diagram below, the total number of human proteome has reached to about 1,000,000 after modification within the cellular environment.
Figure 11-27 Protein [view large image]

Secondary Sturcture - The secondary structure of a protein comes about when the poly-peptide chain takes a particular orientation in space. One common arrangement of the chain is the alpha helix, or right-handed coil, with 3.6 amino acids per turn. Hydrogen bonding between amino acids stabilizes the helix. Another type of secondary structure is known as the beta-pleated sheet. Such polypeptide chains are held together side by side by hydrogen bonds between the peptide chains. A protein can consist of alpha helix, beta-pleated sheet, or a mixture of the two types. The amino acids Alanine, Cysteine, Glutamic Acid, Glutamine, Histidine, Leucine, Lysine, and Methionine are found in alpha helix region; while Arginine, Aspartic Acid, Asparagine, Proline, Serine, and Valine are found in beta-pleated sheets. The loops link these structures together forming a whole.

Loops - Loops are found on the outside of the protein and rich in hydrophilic sidechains. They make hydrogen bonds with the surrounding water more than with adjacent amino acids, and thus are more flexible than helices and sheets. Beside serving as link, they are often involved in the function of the protein, such as being part of the active site of an enzyme, or the binding site of a ligand or receptor. The one in the diagram on the left is called hairpin loop locating at the cell membrane. It is a special case of a turn (where the peptide chain reverses its overall direction), in which the direction of the protein backbone reverses and the flanking secondary structure elements interact.

Alpha Helix - There is a limited number of ways by which secondary structure elements can form. Alpha helix is one of the three motifs. The helix is mostly right-handed, its shape is maintained by the hydrogen bonds between the hydrogen in every backbone N-H group with the oxygen in the backbone C=O group of the amino acid located three or four residues (residue refers to the specific amino acid that is incorporated into a protein chain) earlier along the protein sequence (Figure 11-16, and 11-27,c). A length of about 0.5 nm completes one turn of the helix, i.e., one turn per 3.6 residuals or 4 x 3.6 ~ 13 atoms. A typical helix contains about ten amino acids (the range is about 4 - 40). As much as 80% of a ptotein can be helical, and only a few proteins (~ 7) are known that have no helix whatsoever.

Beta Sheets - Beta sheets consist of strands (each one contains 3 to 10 amino acids) connected laterally by at least two or three backbone hydrogen bonds. The sheets can be arranged in paralell (same N

C directions) or anti-paralell directions. The hydrogen bonds are between the hydrogen in every backbone N-H group and the oxygen in the backbone C=O group of the amino acid as shown in Figure 11-27c. The parallel arrangement is less stable because the geometry of the individual amino acid molecules forces the hydrogen bonds to occur at an angle, making them longer and thus weaker. Contrarily, in the anti-parallel arrangement the hydrogen bonds are aligned directly opposite each other, making for stronger and more stable bonds. On the other hand, alpha helix is more stable then beta sheets because the hydrogen bonds are within the same sequence of backbone, i.e., the interaction is intra-strand.

Tertiary and Quaternary Structures - The tertiary structure of a protein is its final three-dimensional shape. The tertiary shape of a protein is maintained by various types of bonds between the R groups including covalent, ionic, and hydrogen bondings. When two or more polypeptide chain interweave to form one molecule, the protein has a quarternary structure. The protein folds to the state

		of minimum energy (Figure 11-28a). Its sequence has to produce an unique configuration to be useful for living organism. The final shape of a protein is very important to its function. When proteins are exposed to extreme heat and pH, they undergo an irreversible change in shape called denaturation. The change occurs because the normal bonding between the R groups has been disturbed. Once a protein loses its normal shape, it is very difficult to re-generate its usual
Figure 11-28a Protein Folding [view large image]	Figure 11-28b Denaturation [view large image]	function (Figure 11-28b). The atoms in the backbone are held together by covalent bonds making them ten times harder to break.

It is known that even if the gene can code a correct sequence of amino acids and the ribosome can translate the coding without error, the resulting protein can misfold and cause serious problem for the organism. As shown in Figure 11-28a, it seems that the repulsion between some key residues (a recurring unit in a polymer chain such as the amino acid in protein) such as the hydrophobic and polar residues is essential to establish a rudimentary native-like architecture (the saddle point in the diagram). Once the correct topology has been achieved, the native structure (the natural conformation of a protein) will then almost invariably be generated during the final stages of folding. There are molecular chaperones in the cell to weed out the misfolded proteins as shown in Figure 11-29a. Failure of this quality-control system entails a variety of diseases including cancer, diabetes, BSE, cystic fibrosis, Alzheimer, and Parkinson. These "protein-misfolding diseases" share the common pathological feature of aggregated misfolded protein deposits.

Figure 11-29a Protein Misfolding [view large image]

A strand of RNA such as the rRNA also trends to fold into a structure similar to a protein. This ability of the RNA has inspired the hypothetical RNA world in considering the origin of life. Such feat originates from the oxygen in the 2' position of the 5-carbon ribose that allows hydrogen bonding with another hydrogen in the sequence (Figure 11-29b,a). The DNA lacks such feature because the "deoxyribose" removes the oxygen in that place. The single-strand RNA can fold up to various shapes, depending on the sequence of its

bases (see rRNA secondary structure in Figure 11-29b,b). The three-dimensional structure is the result from hydrogen bonding between the complementary bases and between other bases [Figure 11-29b,c - rRNA in dark blue (small subunit) and dark red (large subunit); lighter colors represent ribosomal proteins.]. These forces twist the strand into a partial double helix with a tertiary structure. When certain strategic bonds are broken, this usually stable structure untwists to a one-dimensional form, which is more suitable for information transfer.

Figure 11-29b RNA Folding [view large image]

An enzyme is a special kind of protein that accelerates chemical reaction while retains its own structure. A chemical reaction is about two molecules coming together and altering their structures. Firstly they need a chance to approach each other, the frequency of encounter depends on the concentration of the reactants. Then they should have enough kinetic energy to overcome the potential barrier (activation energy), this energy is related to the temperature. Finally, there is a special orientation of the reactants such that the reaction would proceed much faster, sometimes a million folds faster. Such favourable condition can be created with a special material called enzyme or catalyst. The enzyme forces the reactants into a position most suitable to run the reaction. The enzyme itself does not change and can be

	re-used repeatedly (Figure 11-29c,a). For inorganic chemical reactions, enzyme may not be necessary since the inorganic molecules have high degree of symmetry. For organic chemical reaction, the symmetry for the molecules involved is much lower or none at all; therefore, most chemical processes in life depend on the assistance of the enzyme.
Figure 11-29c Catalyses [view large image]	The action of ligand adopts the same lock and key concept. It is a molecule (not protein) that binds to a receptor on the cell membrane and induces a biological or chemical response within the cell (Figure 11-29c,b).

Structural Support: Proteins provide structural support to cells and tissues. For example, collagen is a protein that forms the framework of connective tissue, while keratin is a protein that gives strength to hair, nails, and skin.
Enzymatic Catalysis: Enzymes are proteins that catalyze biochemical reactions in the body. They act as biological catalysts, increasing the rate of chemical reactions that would otherwise occur too slowly to sustain life.
Transport and Storage: Proteins play an important role in the transport and storage of molecules such as oxygen, iron, and lipids. Hemoglobin, for example, is a protein that transports oxygen in the blood, while ferritin is a protein that stores iron in the body.
Hormonal Signaling: Many hormones in the body are proteins, including insulin, growth hormone, and follicle-stimulating hormone. These hormones bind to specific receptors on target cells, triggering a range of physiological responses.
Immune Defense: Antibodies are proteins that are produced by the immune system to identify and neutralize foreign substances such as bacteria and viruses.
Movement: Proteins such as actin and myosin are responsible for muscle contraction, while flagella and cilia are made up of protein fibers that enable movement in single-celled organisms.

Overall, proteins are essential for the proper functioning of living organisms, and any malfunction or deficiency in protein synthesis can have serious consequences for health and survival.