A simple electrostatic criterion for predicting the thermal stability of proteins.
The enhancement of protein thermostability is an important issue for both basic science and biotechnology purposes. We have developed a thermostability criterion for a protein in terms of a quasi-electric dipole moment (contributed by its charged residues) defined for an electric charge distribution whose total charge is not zero. It was found that minimization of the modulus of this dipole moment increased its thermal stability, as demonstrated by surveying these values in pairs of mesostable-thermostable homologous proteins and in mutations described in the literature. The analysis of these observations provides criteria for thermostabilization of a protein, by computing its dipole profile. This profile is obtained by direct substitution of each amino acid of the sequence by either a positive, negative or neutral amino acid, followed by a recalculation of the dipole moment. As an experimental example, these criteria were applied to a beta-glucanase to enhance its thermal stability.
Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Avda. Rovira Roure 44, 25198 Lleida, Spain. angel.mozo@cmb.udl.es
Angel
A
Mozo-Villarías
Juan
J
Cedano
Enrique
E
Querol
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry; D004563:Electrochemistry; D006026:Glycoside Hydrolases / Q000737:chemistry; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D009154:Mutation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012260:Ribonucleases / Q000737:chemistry; D055672:Static Electricity; D044366:Transition Temperature
D000596:Amino Acids; D011506:Proteins; D012260:Ribonucleases; D006026:Glycoside Hydrolases