The Conformational Stability of Proteins: Rational Stabilization by Protein Engineering

Biotecnologia Aplicada 2000; Vol. 17 No. 1, pp. 53 The Conformational Stability of Proteins: Rational Stabilization by Protein Engineering Javier Sancho Sanz Code Number: BA00017 Introduction Proteins are linear polymers that fold into compact conformations in order to acquire the particular shape that confers them useful biological properties. The native conformations of proteins are stabilized by intra protein interactions (hydrogen bonds, van der Waals, charge/charge, charge/dipole, charge/p and p/p) and by the hydrophobic effect, and they are destabilized mainly by the huge conformational entropy change of folding. A delicate balance between all those factors determines that the average stability of proteins is low (5-15 kcal mol-1). Although 5 kcal mol is enough to ensure that more than 99% of the protein molecules are in the native conformation at any time, the equilibrium between native and denatured conformations forces all the molecules to be unfolded now and then. In the absence of side reactions this is not a problem, but the unfolded state and, perhaps even more, some conformations intermediate between the native and the unfolded state can experience aggregation and other reactions leading to an irreversibly inactivated protein. Irreversible inactivation from the folded conformation is also possible but usually less severe. Since the unfolded state has a greater tendency to irreversible inactivation, one way to minimize these reactions is to reduce the concentration of unfolded molecules. This can be easily done by increasing the conformational stability of proteins. Copyright 2000 Elfos Scientia