Engineering protein thermal stability. Sequence statistics point to residue substitutions in alpha-helices.
Amino acid sequences have been compared for thermophilic and mesophilic molecules from six different protein families, which include lactate and glyceraldehyde-3-phosphate dehydrogenases, triose phosphate isomerases, superoxide dismutases, thermolysins and subtilisins. Since a three-dimensional structure was known for at least one of the sequences in each family, analysis of preferred residue substitutions, presumably to achieve thermal stability, could be examined from a structural context. The overall results, which are generally consistent across all the families, suggested decreased flexibility and increased hydrophobicity in alpha-helical regions as the main stabilizing principles. The most favoured residual exchanges, hopefully useful in engineering stability into proteins, are discussed.
Menéndez-Arias
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L
Departmento de Bioquímica y Biología Molecular I, Facultad de Ciencias, Universidad Complutense, Madrid, Spain.
Argos
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D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D001426:Bacterial Proteins; D002645:Chickens; D005656:Fungal Proteins; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D011487:Protein Conformation; D011506:Proteins; D011817:Rabbits; D051381:Rats
D000596:Amino Acids; D001426:Bacterial Proteins; D005656:Fungal Proteins; D011506:Proteins