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AGA: Enzyme

Aspartylglucosaminidase (AGA) enzyme normal function:
Its function is proteolytic, degrading glycoprotein via hydrolytic deglycosylation. Formally classed as a hydrolase (EC 3.5.1.26), it is a member of a family called the Ntn (N-terminal nucleophilic) hydrolases. These enzymes are characterized by coding as a large pre-protein and are post-translationally cleaved by autoproteolysis to create α- and β-subunits and a new N-terminal amino acid. The heterotetrameric AGA enzyme has two active sites, consisting of an essential conserved β-chain N-terminal threonine within an active site of deep conical profile. The enzyme is novel in that it requires both the α-amino and the α-carboxyl group of the substituted amino acid residue to be free. Additionally, the same Thr residue is involved both in genesis of the active enzyme, and in catalytic function of the active site.
 

AGA Gene mutation:
Over 30 mutations in AGA gene have been found to cause aspartylglucosaminuria.
Most of these mutations change one amino acid in aspartylglucosaminidase. One mutation, found in 98% of people with this condition in Finland, replaces the amino acid cysteine with the amino acid serine at position 163 in the enzyme (written as Cys163Ser or C163S). Many mutations, including C163S, disrupt the proper folding of the enzyme, resulting in an AGA enzyme that cannot effectively break down glycoproteins. A buildup of glycoproteins seems to particularly affect nerve cells in the brain; loss of these cells causes a progressive decline in mental functioning and the other signs and symptoms of the disease.