The stability of proteins and nucleic acids
المؤلف:
Peter Atkins، Julio de Paula
المصدر:
ATKINS PHYSICAL CHEMISTRY
الجزء والصفحة:
681
2025-12-18
61
The stability of proteins and nucleic acids
The loss of their natural conformation by proteins and nucleic acids is called denaturation. It can be achieved by changing the temperature or by adding chemical agents. Cooking is an example of thermal denaturation. When eggs are cooked, the protein albumin is denatured irreversibly, collapsing into a structure that resembles a random coil. One example of chemical denaturation is the ‘permanent waving’ of hair, which is a result of the reorganization of the protein keratin in hair. Disulfide cross-links between the chains of keratin render the protein and, hence hair fibres, inflexible. Chemical reduction of the disulfide bonds unravels keratin, and allows hair to be shaped. Oxidation re-forms the disulfide bonds and sets the new shape. The ‘per manence’ is only temporary, however, because the structure of newly formed hair is genetically controlled. Other means of chemically denaturing a protein include the addition of compounds that form stronger hydrogen bonds than those within a helix or sheet. One example is urea, which competes for the NH and CO groups of a poly peptide. The action of acids or bases, which can protonate or deprotonate groups involved in hydrogen bonding or change the Coulombic interactions that determine the conformation of a protein, can also result in denaturation.
Closer examination of thermal denaturation reveals some of the chemical factors that determine protein and nucleic acid stability. Thermal denaturation is similar to the melting of synthetic polymers (Section 19.9). Denaturation is a cooperative process in the sense that the biopolymer becomes increasingly more susceptible to denaturation once the process begins. This cooperativity is observed as a sharp step in a plot of fraction of unfolded polymer versus temperature (Impact I16.1). The melting temperature, Tm, is the temperature at which the fraction of unfolded polymer is 0.5 (Fig. 19.37). A DNA molecule is held together by hydrogen bonding interactions between bases of different chains and by base-stacking, in which dispersion interactions bring together the planar π systems of bases. Each G-C base pair has three hydrogen bonds whereas each A-T base pair has only two. Furthermore, experiments show that stack ing interactions are stronger between C-G base pairs than between A-T base pairs. It follows that two factors render DNA sequences rich in C-G base pairs more stable than sequences rich in A-T base pairs: more hydrogen bonds between the bases and stronger stacking interactions between base pairs. Proteins are relatively unstable towards chemical and thermal denaturation. For example, Tm = 320 K for ribonuclease T1 (an enzyme that cleaves RNA in the cell), which is not far above the temperature at which the enzyme must operate (close to body temperature, 310 K). More surprisingly, the Gibbs energy for the unfolding of ribonuclease T1 at pH 7.0 and 298 K is only 19.5 kJ mol−1, which is comparable to the energy required to break a single hydrogen bond (about 20 kJ mol−1). Therefore, unlike DNA, the stability of a protein does not increase in a simple way with the number of hydrogen bonding interactions. While the reasons for the low stability of proteins are not known, the answer probably lies in a delicate balance of all intra- and intermolecular interactions that allow a protein to fold into its active conformation, as discussed in Section 19.10.
Fig. 19.37 A protein unfolds as the temperature of the sample increases. The sharp step in the plot of fraction of unfolded protein against temperature indicated that the transition is cooperative. The melting temperature, Tm, is the temperature at which the fraction of unfolded polymer is 0.5.
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