Glycoside hydrolase 131 catalytic N-terminal domain. This is the N-terminal domain found in glycoside hydrolase family 131 (GH131A) protein observed in Coprinopsis cinerea. GH131A exhibits bifunctional exo-beta-1,3-/-1,6- and endo-beta-1,4 activity toward beta-glucan. This domain is catalytic in nature though the catalytic mechanism of C. cinerea GH131A is different from that of typical glycosidases that use a pair of carboxylic acid residues as the catalytic residues. In the case of GH131A, Glu98 and His218 may form a catalytic dyad and Glu98 may activate His218 during catalysis.
Atrophin-1 family. Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.
