Most of the major molecules of the cell - whether structural, like cellular equivalents of a building’s girders and beams, or mechanical, like enzymes that take apart or put together other molecules, are proteins. Proteins interact with a wide variety of other molecules, though any given interaction is usually quite specific. The specificity is determined in part by electrical attraction between the molecules. So, what determines the charge of different regions of a protein?
Amino acids (Figure 9), which are joined together to make proteins, may be positively charged (basic), negatively charged (acidic), polar, or nonpolar, based on the characteristics of their side chains. The charge on the amino or carboxyl end of each amino acid does not play a role in the overall character of any particular region of the protein, because they are effectively neutral, having been linked, the amino group of one amino acid to the carboxyl group of another, by a peptide bond. Note the Figure of the amino acid: it is one carbon, called the a carbon, linked to amino and carboxyl groups on opposite sides, and to hydrogen, and a side chain, denoted by R. These side chains, of which there are twenty common ones, can be as simple as a hydrogen atom (glycine), or could be quite complex, involving extended ring structures (histidine, phenylalanine). The variety in their size, shape, and charge all add up to an extremely versatile set of building blocks for some of the most important working molecules of the cell.
Almost all amino acids (glycine is the exception) are optically active, which means that they are asymmetric in such a way that it is impossible to superimpose the original molecule upon its mirror image. There is a “handed-ness” about them, much as your right hand cannot be superimposed on your left hand if both palms must face the same direction. In fact, in the Figure here, you can also understand why glycine is an exception, since its R-group is a simple hydrogen atom.
Chiral pairs, or enantiomers, not only have the same atomic components like all isomers, they also have the same bonds and bond order. The term “optically active” comes from the discovery that polarize light is rotated in different directions by enantiomers. Amino acids are often labeled as either d- (dextrorotatory) or l- (levorotatory) depending on their atomic configuration in relation to the enantiomers of glyceraldehyde. This is a common naming system, but not always logical, in that almost half of the l-amino acids are in fact dextrorotatory (clockwise rotation of light), but their molecular configurations resemble the levorotatory isomer of glyceraldehyde.
Ribosome-created proteins and peptides are all constructed with l-amino acids. However, d-amino acids do exist in nature, and can be incorporated into peptides through non-ribosomal means. An excellent example is found in the cell walls of some bacteria. Because most proteolytic enzymes only act on proteins with lamino acids, the incorporation of d-amino acids into the cell wall can protect the bacteria from harm. These D-amino acids are incorporated by transpeptidase. Transpeptidase is also the target of the antibiotic, penicillin, which is an irreversible inhibitor of that enzyme.
In the cell, a peptide bond is formed between two amino acids with enzymatic help from the ribosome. Like the previous two polymerizing reactions, formation of peptide bonds is a condensation reaction in which the carbon of the carboxyl group and the nitrogen from the amino group of their respective amino acids are bonded together (Figure 10). This is a very stable bond due to resonance of the amide group. In the cell, peptide bonds are mostly nonreactive, except when attacked by proteolytic enzymes.
A peptide is an inexact term used for relatively few (usually <30) amino acids joined together. Each amino acid in a polypeptide or protein may also be referred to as a “residue” which can sometimes be confusing because the same term is also applied to monomers of nucleic acids and of polysaccharides. Larger polymers are known as polypeptides or as proteins, although polypeptide has more of a structural connotation and may be used to indicate an unfinished or not-yet-functional state, whereas protein generally implies some physiological function. On of the key characteristics of proteins is the ability to form secondary, tertiary, and for proteins, quaternary structure by means of specific folding patterns. If you think of a long piece of thread, yarn, or rope, you can probably imagine an infinite number of different ways to arrange it, from spirals to loops to random tangles. This is essentially what can happen with a protein with the constraints put upon it by the size and charge of the amino acids that compose it.
The primary structure of a protein is simply the sequence of amino acids that compose the protein. These amino acids are joined by peptide bonds from the carboxyl terminal of one amino acid to the amino terminal of the next. Secondary structure refers to the localized, simple, shapes that can be formed, such as alpha-helices, or beta-sheets. These come about primarily through hydrogen bonding to nearby (relative to the primary structure) residues.
Tertiary structure is 3-dimensional structure that is built upon arrangements of second ary structures, often through disulfide bonds and hydrophobic interactions in addition to hydrogen bonding. In the context of structural stability, cysteine plays a special role. Beyond the primary structure, most protein folding is held in place by hydrogen bonds. Although strong enough in most situations, they can be disrupted without extraordinary energy. Disulfide bonds ( —S—S—) are covalent bonds that form between the sulfhydryl groups of two cysteines that effectively locks the local protein structure in place, making the protein extremely stable.
Finally, quaternary structure is the arrangement of different individual polypeptides (subunits) into a functional protein. Obviously, only multi-subunit proteins have a quaternary structure.