13. The β-hexosaminidase story in Toronto: From enzyme structure to gene mutation

Abstract

This chapter discusses the structure of Hexosaminidase A and Hexosaminidase B. It was found that while the β subunits of Hex A and Hex B contained two polypeptides of 25–30 kDa, the β subunit of Hex A was composed of a single chain of 50–60 kDa.A and Hex B did contain two polypeptides of 25–30 kDa, the β subunit of Hex A was composed of a single chain of 50–60 kDa. The reduced and alkylated Hex A and Hex B are separated on isoelectric focusing slab gels (IEF-PAGE), run in urea and detergent, and the polypeptide chains forming the β subunit in both isozymes could be separated in an acidic group and a basic group of heterogeneous bands. The chapter also discusses isolation of cDNA clones coding for α and β chains, homology between the deduced α and β primary structures, posttranslational processing of the pre-pro-α and pre-pro-β chains, structure–function relationships, and molecular heterogeneity in Tay-Sachs and Sandhoff Diseases.