Several of the amino acidA carboxylic acid containing an amino group (-NH2). In an alpha amino acid, the amino group is attached to the carbon atom adjacent to the carboxyl group. side chains are difficult to fit into either the α helix or β-sheet types of structure. An obvious example is proline, in which the R groupThose elements that comprise a single column of the periodic table. Also called family. is a ring and includes nitrogen bonded to the α carbon. When proline is involved in a peptide bondThe amide linkage that joins the carboxylic acid end of one amino acid with the amine end of another amino acid to form a peptide or protein., all hydrogens are gone from the nitrogen, leaving no site for hydrogen bonding.
Another problem involves side chains having the same charge, such as those of lysine and arginine or glutamic acid and aspartic acid, which repel one another considerably. When they occur close together, these groups may also destabilize an α helix or β sheet structure. The presence of several groups of the type just mentioned allows a proteinA biological polymer of amino acids joined by peptide bonds. chain to bend sharply instead of laying flat or curling regularly into a spiral. Such sharp bends connect sections of α helix or β sheet structures in the globular proteins. They allow the polypeptideA polymer of many amino acids joined by amide linkages or "peptide bonds." chain to curl back upon itself, folding the protein into a very compact, nearly spherical shape. The nature of this folding is referred to as tertiary structureThe manner in which the sheets and helices of the secondary structure of a protein fold on themselves to define the three-dimensional structure; tertoaru structure is maintained by hydrogen bonds, dipole forces, ionic attractions, covalent bonds, and, most importantly, hydrophobic interactions., since it involves a third organizational level above the primary amino acid sequence and the secondary α helix or β sheet.
Several other important generalizations may be made about the structure of myoglobin. Even in regions where the chain twists into an α helix, nearly all the nonpolarDescribes a molecule with no net permanent dipole; this can occur when there is no separation of centers of positive and negative electrical charge or because there are bond dipoles that cancel each others' effects. A polar molecule will assume certain orientations more than others in an electric field. R groups point toward the interior of the moleculeA set of atoms joined by covalent bonds and having no net charge.. Here they crowd so closely together that only four water molecules can squeeze their way in. The outside surface of the protein, however, contains all the polar R groups. These interact strongly with the many water molecules which normally surround myoglobin in muscle tissue.
Although myoglobins isolated from a variety of mammals differ slightly in their primary structureThe sequence of amino acids that defines a protein., they all seem to have nearly the same overall molecular shape. Apparently some of the amino acids are much more important than others in determining the bend points and other crucial features of tertiary structure. Substitutions at less-important positions do not cause great variations in the ability of the protein to carry out its biological function.
Finally, figure 1 shows clearly that myoglobin contains a prosthetic group. In this case it is the heme group, which contains an iron atom surrounded by four nitrogens in a flat ring structure known as a porphyrin. The porphyrin ring is not covalently bonded to the protein chain, but rather fits snugly into a “pocket” surrounded by several segments of helix. A nitrogen atom in a histidine side chain on one helix does form a coordinate covalent bondA bond between two atoms in which the shared electrons are considered to be contributed by only one of the atoms. with iron in the heme group, but apart from this the prosthetic group is positioned solely by the way the protein chain is folded.
The iron in the heme group marks the active siteThe location where catalysis occurs in an enzyme or other catalyst. at which the oxygen-storage function of myoglobin is accomplished. Iron, like other first-row transition-metalAn element characterized by a glossy surface, high thermal and electrical conductivity, malleability, and ductility. ions, ordinarily forms six bonds directed toward the corners of an octahedron. In myoglobin only five bonds to iron are found. The sixth position (opposite the histidine nitrogen) can be occupied by an oxygen molecule, providing a convenient storage site. If the concentrationA measure of the ratio of the quantity of a substance to the quantity of solvent, solution, or ore. Also, the process of making something more concentrated. of oxygen near the protein falls, this binding is reversed, releasing oxygen to replenish the supply.
If an iron ion can bond to an oxygen molecule, you may wonder why the complicated porphyrin and protein structures are necessary. It is to prevent the oxidationThat part of a chemical reaction in which a reactant loses electrons; simultaneous reduction of a reactant must occur. of the iron in the heme group from the iron(II) to the iron(III) oxidation stateA formally defined charge that an atom in a compound or ion would have if the compound or ion consisted entirely of monatomic ions. Based on a Lewis diagram, the charge that an atom would have if all electrons in bonds were assigned to the more electronegative atom or divided equally between atoms of the same electronegativity.. Because the oxygen molecule needs to gain two electrons to be oxidized while iron(II) can only supply one, no electron transfer occurs. If the iron(II) atom in heme were not surrounded by the protein chain, a water molecule would be able to take part as an intermediateIn chemical kinetics, a species that is formed in an early step in a reaction mechanism and then consumed in a later step; evidence of existence of an intermediate may be important for the interpretation of a rate law. in the electron-transfer mechanism and reductionThat part of a chemical reaction in which a reactant gains electrons; simultaneous oxidation of a reactant must occur. of the oxygen could occur. As matters stand, though, the oxygen molecule cannot be reduced until it is released by the myoglobin. Thus the combined effects of the tertiary structure of the protein, the prosthetic group, and a specialized active site allow the myoglobin to fulfill its biological function of storing oxygen molecules until needed, without allowing them to be reduced during storage.
In some proteins there is yet a fourth level of organization, labeled quaternary structureThe manner in which the major subunits, each consisting of a separate polypeptide chain, of a large protein are joined together.. This may be illustrated by hemoglobin, whose function as an oxygen carrier in the bloodstream is well known. Hemoglobin consists essentially of four myoglobin molecules packed together in a single unitA particular measure of a physical quantity that is used to express the magnitude of the physical quantity; for example, the meter is the unit of the physical quantity, length.. Four separate polypeptide chains are each folded as in myoglobin and then nested together. The way these four subunits fit together constitutes the quaternary structure.
Like the other type of structures, quaternary structure contributes to the function of a protein. In the case of hemoglobin, an oxygen molecule attached to one subunit causes slight shifts in tertiary and quaternary structure which make it easier for other oxygen molecules to bond to the other subunits. Consequently hemoglobin in the lungs can be loaded with its full complement of four oxygen molecules rather easily, a factor which increases its efficiency in carrying oxygen to body tissues. The converse is also true—loss of one oxygen molecule causes slight structural rearrangements which allow the remaining three to depart more readily.