Proteins

Proteins serve as the machinery and much of the structure in living organisms - they do most of the jobs. [overhead - one million times magnification, protein Plate 7] Functionally we can categorize proteins into three broadly defined groups based on their functions:

• Structural proteins.
• Recognition proteins.
• Enzymes.

Protein Structure: In order to understand and categorize their organization, protein structure has been divided into four hierarchical levels and a couple of sublevels:

• Primary structure (1°) : the linear order or sequence of peptide bonded amino acid residues, beginning at the N-terminus. (Characteristic bond type: covalent.)
• Secondary structure (2°): the steric relations of residues nearby in the primary structure which give rise to local regularities of conformation. These structures are maintained by hydrogen bonds between peptide bond carbonyl oxygens and amide hydrogens. The major secondary structural elements are the a-helix and the b-strand. (Characteristic bond type: hydrogen.)
• Tertiary structure (3°): the steric relations of residues distant in the primary sequence; the overall folding pattern of a single covalently linked molecule. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals, disulfide.) Tertiary structures often exhibit intermediate recognizable patterns of folding:
  • Domains: independent folding regions within a protein, usually sequences of a bit over one hundred residues. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.)
    • Super secondary structure (motifs): defined associations of secondary structural elements. (Characteristic bond type: hydrogen & hydrophobic.)
• Quarternary structure (4°): the association of two or more independent proteins via non-covalent forces to give a multimeric protein. The individual peptide units of this protein are referred to as subunits, and they may be identical or different from one another. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.)

Proteins are of particular interest to us because most toxins act through their interactions with proteins. To understand these interactions we must first review and look at bonding. In General chemistry you learned about covalent and ionic bonds. Both of these are considered strong bonds. Some typical covalent bonds important in biological systems and their strengths are: C-C @ 80 kcal/mole, O-H @ 110 kcal/mole, and S-S @ 40 kcal/mole. Ionic bonds have similar strengths in vacuo but do not have directionality and are non-specific. Contrast the situation for ionic bonds in aqueous solutions in the table, the insulating qualities (dielectric strength) of water vastly reduces the bond strength.

Interaction Type Example Average Strength, kcal/mol (kJ/mol) Range** Charge-charge (ionic) -NH3+ Cl-   1/r Charge-dipole -NH3+ClCH3   1/r2 Dipole-dipole ClCH3 ClCH3    1/r3 Dipole-induced dipole* CH4 ClCH3 0.1-0.2 (0.4-4)  1/r6 Dispersion* (induced dipole-induced dipole) CH4 CH4 0.1-0.2 (0.4-4) 1/r6 Hydrogen bond   3-8 (12-30)    van der Waals repulsion     1/r12 *van der Waals interactions, **from Zubay Biochemistry 3rd. (1993) Table 4.3, pg. 89.

Note that the van der Waals types of forces are essentially contact forces, proportional to the surface areas in contact, and with little action at a distance due to the rapid 1/r⁶ fall off. Even though weak these bonds can be important in macromolecules because the large surface areas involved can result in reasonably large total forces. However, there must be a close fit. They can also be important for helping to bind organic molecules to surfaces on macromolecules like proteins.

Next we need to look at hydrogen bonds. In this case strongly polarized bonds between hydrogen and a small, very electronegative atom (N, O, or F) allow a strong dipole-dipole bond to be formed with another small very electronegative element (N, O, or F). Importantly, the very small sizes of these particular elements also allow them to approach each other so closely that a partial covalent bond is also formed (e.g. O-H---N). Note that the partial covalent character means that these bonds (H-bonds) are directional and strongest when the nuclei of all three involved atoms are in a linear arrangement.

Finally, the hydrogen bonding in water leads to another kind of force which is extremely important in biological systems. In water each molecule is potentially bonded to four other water molecules through H-bonds. If a non-polar molecule, which cannot participate in H-bonding nor in electrostatic interactions with the water molecules, is inserted into water a number of H-bonds will be broken and not replaced. Thus there will be an energy cost to putting non-polar molecules into water, and water will attempt to force these molecules out of solution to minimize the surface of contact and thus the number of H-bonds which are broken (there are also significant entropy considerations which we will not deal with here). So, when you mix oil and water, as in a vinegar and oil dressing, the oil tends to separate out fairly quickly, not because the oil molecules "want to get together," but because the water forces them out. [overhead V&V 7-51, 2-7]This so-called hydrophobic force is one of the most important in maintaining the shapes of proteins, in holding proteins together to make structures such as muscle, to form and maintain membranes and to hold together molecules such as the DNA double-helix.

Last modified 28 January 2010

© RA Paselk 2001