Deficiencies in the enzymatic activity of acid sphingomyelinase (ASM) result in Niemann-Pick disease. A variety of modifications which eliminate the activity of the free thiol on the C-terminal cysteine residue of ASM all result in substantially increased specific activity of the enzyme. Methods used to alter the activity of this residue include site-directed mutagenesis to delete or alter the residue, enzymatic degradation of the ASM to remove the residue, copper-promoted dimerization of ASM (via the terminal cysteine residues) and chemical modification of the free thiol group on this residue.
酸性鞘
磷脂酶(ASM)的酶活性不足会导致尼曼-皮克病。 消除 ASM C 端半胱
氨酸残基上游离
硫醇活性的各种修饰都能显著提高酶的特异性活性。 用于改变该残基活性的方法包括:定点突变以删除或改变该残基、酶降解 ASM 以去除该残基、
铜促进 ASM 的二聚化(通过末端半胱
氨酸残基)以及对该残基上的游离
硫醇基团进行
化学修饰。