A BRIEF DISCUSSION ON THE STRUCTURE, FUNCTIONS AND IMPORTANCE OF

Proteins
The amount of amino acids that can be linked together may vary from 2 (dipeptide) to a thousand (polypeptide), and the resulting sequence of amino acids denotes the primary level of protein structure. This resulting sequence is also responsible for the formation of higher-order structures. Furthermore, the naming of the residues (amino acid units) in the chain starts at the amino end or N terminus by convention. Peptide bonds are planar due to resonance: a pair of bonding electrons in the carbonyl (C=O) group may delocalize towards the carbonyl carbon and the nitrogen of the amino group to form C=N. So in effect, a peptide bond is rigid. However, the bonds adjacent to it arent; this means that residues may rotate about the carbon carbonyl carbon and carbonnitrogen bonds. The resulting dihedral angles are called psi () and phi (), respectively, and both angles can be used to visualize the possible conformations of secondary structures (sterically allowed or otherwise). The distribution of possible regular conformations in a polypeptide chain is referred to as the secondary structure. The formation of secondary structures is greatly affected by molecular geometry and atomic interactions. Conformations include helices, sheets, turns and loops. helices are rodlike structures comprising a tightly-coiled backbone in the center with the side chains sticking outward. Intrachain hydrogen bonding between the carbonyl and amino groups in the backbone is primarily responsible for the formation of this structure. A turn is defined as the portion of the chain bounded by the amino and carbonyl groups that are bonded noncovalently; a right-handed helix contains 3.6 residues per turn, with 13 atoms forming an imaginary loop (hence the designation 3.613). sheets, on the other hand, are polypeptide strands linked together via interchain hydrogen bonding between the aforementioned functional groups. 4, 5, or even more than 10 strands can be arranged in a parallel or antiparallel fashion, or a combination of both.
1

he genetic information of the cell is expressed through proteins. This biomolecule is composed of repeating units called amino acids. An amino acid contains a carbon atom ( carbon) with four different groups attached to it: an amino group, a carboxyl group, a hydrogen atom and an R group (except for glycine which uses a second hydrogen atom in lieu of an R group). Hence, amino acids exhibit chirality. Both D (dextrorotatory) and L (levorotatory) isomers of amino acids exist in nature, but only L-amino acids are found in proteins. The 20 amino acids can be categorized into five groups: nonpolar, polar, aromatic, positively charged and negatively charged. These amino acids are grouped with respect to the side chains. Essential amino acids are amino acids that cannot be synthesized by the body (and are consequentially obtained from dietary sources). Essential amino acids include threonine, valine, methionine, isoleucine, leucine, lysine, phenylalanine, tryptophan, histidine and arginine. Another unique feature of amino acids is their ability to dissociate as ions (or ionize) in neutral aqueous environments. Thus, they can function as both acid and base, and such substances are called ampholytes. Under physiological conditions, the amino group becomes protonated (gains one H+) while the carboxyl group becomes deprotonated (loses one H+); this ionic form is referred to as the zwitterion. Amino acids that are joined at the nitrogen atom of the amino group and the carbon atom of the carboxyl group are called peptides. The linkages are obtained from the condensation of individual amino acids resulting in the liberation of a water molecule for every bond formed, and the bond is called a peptide bond. The reverse reaction (hydrolysis) is thermodynamically favored over condensation and can be achieved through the presence of enzymes (specifically proteases) or a strong acid or base at high temperatures.

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PROTEINS

Figure 1: D (right) and L isomers of amino acids

Figure 2: Counterclockwise arrangement of substituents in an L amino acid from highest to lowest priority

Figure 3: Positively charged side chains

Figure 4: Polar side chains

Figure 5: Aromatic side chains

Figure 6: Negatively charged side chains ajasolidum@mapua.edu.ph

Figure 7: Nonpolar side chains

PROTEINS

Reversals in direction within the polypeptide chain are facilitated by turns and loops. These structures are found on the surface of proteins; therefore, one can expect the participation of turns and loops in interactions between proteins and other molecules. Turns are characterized by the relatively small amount of residues involved in the formation of the structure. The common turn contains two residues sandwiched between two terminal residues that are linked via backbone hydrogen bonding. The turn, on the other hand, replaces the two residues in the middle with proline, which makes the reversal more abrupt. Loops are more elaborate chain reversal components that do not exhibit regular, periodic structures. Secondary structures can be combined to form special kinds of structures which can impart specific functions to the protein. Such formations are called supersecondary structures. Examples include the leucine zipper, zinc finger and Greek key. A particular secondary structure can be linked repeatedly to form proteins that are elongated. These consolidated structurescalled fibrous proteinshave structural roles. Keratin in the nails and hair are composed of fibers that are made of bundles of intertwined helices; two helices that are twisted together form a coiled coil. Another kind of fibrous protein is silk fibroin, which is produced by the silkworm Bombyx mori. Silk fibroin is composed of sheets stacked on top of one another via interdigitation of small side chains, resulting in a structure that is strong (due to the hydrogen bonding within the antiparallel sheets) yet flexible (because of the van der Waals interactions between the glycine and alanine/serine side chains). Collagen, on the other hand, is made of fibers that were generated by crosslinking and modifying triple helices. Collagen is a major constituent of the skin, bones and tendons, and it is also regarded as the most abundant protein in vertebrates. The major difference between globular and fibrous proteins, aside from the presence of more than one type of secondary structure in the former, is the definite three-

dimensional arrangement of atoms in globular proteins. A polypeptide chain can be folded into a compact structure, often folding locally to form an assortment of secondary structures which would then fold on one another to compress the protein and generate recognizably distinct functional regions (domains). The tertiary structure of proteins pertains to the aforementioned folding of the polypeptide. A globular protein is folded in such a way that the hydrophilic regions remain on the surface while the hydrophobic regions are safely tucked inside. Many globular proteins contain small molecules that may be bonded to the protein covalently or noncovalently. These molecules are called prosthetic groups, and they impart special functions to the protein. Classes of proteins which contain such groups include phosphoproteins (phosphates), lipoproteins (lipids), glycoproteins (carbohydrates), hemoproteins (iron porphyrin, also known as heme), flavoproteins (riboflavin-derived nucleotides), nucleoproteins (DNA or RNA) and metalloproteins (metal ions such as Fe2+ and Zn2+). The tertiary structure of a protein is dictated by its polypeptide sequence. Folding is a thermodynamically favored process; therefore, the overall change in free energy (G) should be negative. Conformational entropy pertains to the decrease in randomness brought about by the formation of folded structures, therefore corresponding to a negative overall change in entropy (S). However, according to the free energy equation (G = H TS), the conformational entropy will increase the free energy and disfavor folding. The presence of internal interactions and the so-called hydrophobic effect will help counteract this adverse effect. Formation of internal interactions such as van der Waals, charge-charge and hydrogen bonding interactions would lead to an overall decrease in enthalpy (H). When the polypeptide starts to fold, an increase in molecular randomness can be generated by the disappearance of exposed hydrophobic regions; thus, the so-called hydrophobic effect also contributes to an increase in entropy. These three thermodynamic factors can be combined to generate an overall decrease in free energy.

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PROTEINS

Figure 8: The various ionized forms of an amino acid Figure 9: Dihedral angles

Figure 11: Parallel (top) and antiparallel (bottom) sheets

Figure 10: Ball and stick model of an helix

Figure12: Loops (magenta)

Figure 13: Ramachandran plot

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PROTEINS

Research shows, however, that even though the folding process starts with an unfolded protein, it doesnt stop after the native (folded) state has been attained. In other words, the final state would still rearrange itself constantly. This illustrates the complexity of protein folding in vivo (in living systems). Folding is actually aided by enzymes and small proteins (called chaperone proteins) which facilitate the proper assembly of protein structures by preventing premature and improper associations or by providing assistance during the folding process. The convoluted structures of globular proteins can also be disrupted by various factors. When proteins become denatured, they lose their structure as well as the function that is linked to the said structure. Denaturation can be brought about by changes in the environment such as an increase in temperature, abrupt changes in pH, and the introduction of other molecules that can disrupt the native conformation of the polypeptide (e.g. detergents). A globular protein can be combined with proteins of its own kind or even with different proteins to form quaternary structures called multisubunit proteins. In

essence, multisubunit proteins contain more than one polypeptide chain. Homotypic protein-protein interactions involve only one kind of tertiary structure whereas heterotypic protein-protein interactions involve at least two different subunits. Homotypic interactions can be further broken down into heterologous and isologous interactions. Heterologous interactions are aptly-named because the interacting sites are opposite one another. Isologous interactions follow the same principle but the subunits are arranged in such a way that the resulting structure will feature at least one axis or plane of symmetry. Proteins have several functions. Fibrous proteins, for example, can be used for structural support. Contractile systems like the actin-myosin filaments found in muscle fibers are also made of proteins. Proteins are also used to transport and store various molecules such as oxygen (in the case of hemoglobin and myoglobin). A group of proteins called nonhistone chromosomal proteins regulate cellular activity. And enzymes mediate chemical reactions in physiological systems while immunoglobulins defend the body by using highly variable domains to bind onto various antigens and generate an immune response throughout the body.

Figure 16: Keratin and its structural sublevels Figure 14: 3D ball and stick model (a) and 2D cross-sectional view (b) of silk fibroin

Figure 15: Collagen formation

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REFERENCES Mathews and van Holde (1996). Biochemistry (2nd ed). The Benjamin/Cummings Publishing Company, Inc. Berg, Tymoczko and Stryer (2006). Biochemistry (6th ed). W. H. Freeman, Inc. http://www.nd.edu/~aseriann/silk.html http://jeffreydach.com/2008/11/27/heart-disease-ascorbate-lysine-and-linus-pauling-by-jeffrey-dach-md.aspx http://www.biology.iupui.edu/biocourses/biol540h/ebroberts.html

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PROTEINS