HELIX STABILIZING FACTORS AND STABILIZATION OF THERMOPHILIC PROTEINS - AN X-RAY BASED STUDY

We have compared the X-ray structures of 13 thermophilic proteins with their mesophilic homologues, in order to bring out differences in the stability of helices. The energy terms of a helix-coil transition alg orithm were used to evaluate helix stability. Helices of thermophilic proteins are more stable than the mesophilic homologues in 69% of case s. This is due mainly to intrinsic helical propensities of amino acids , whereas minor effects are linked to main chain II-bonds, side chain- side chain interactions, capping motifs and charge-dipole effects. Fur thermore, the frequency of 10 helix stabilizing factors recognized by appropriate sequence patterns was evaluated. The only factor occurring significantly in the thermostable proteins was the lack of beta branc hed residues. Other factors do not show a definite trend, although the ir occurrence in proteins is believed to be important for stability. T his is discussed in the light of protein engineering applications.