THE STRUCTURE, STABILITY, AND FOLDING PROCESS OF AMYLOIDOGENIC MUTANTHUMAN LYSOZYME

The physicochemical properties of an amyloidogenic mutant human lysozy me (Ile56Thr) were examined in order to elucidate the mechanism of amy loid formation, The crystal structure of the mutant protein was the sa me as the wild-type structure, except that the hydroxyl group of the i ntroduced Thr56 formed a hydrogen bond with a water molecule in the in terior of the protein. The other physicochemical properties of the mut ant protein in the native state were not different from those of the w ild-type protein, However, the equilibrium and kinetic stabilities of the mutant protein were remarkably decreased due to the introduction o f a polar residue (Thr) in the interior of the molecule, It can be con cluded that the amyloid formation of the mutant human lysozyme is due to a tendency to favor (partly or/and completely) denatured structures .