P Durand, Lehn, P, Callebaut, I, Fabrega, S, Henrissat, B and Mornon, JP (1997), "Active-site motifs of lysosomal acid hydrolases: invariant features of clan GH-A glycosyl hydrolases deduced from hydrophobic cluster analysis.", Glycobiology, 7, 2: 277-84.
Abstract: The clan GH-A is a group of more than 200 proteins representing
nine established families of glycosyl hydrolases that act on a large
variety of substrates. This clan includes five enzymes implicated
in lysosomal storage diseases: beta-glucuronidase (Sly disease),
beta-glucocerebrosidase (Gaucher disease), beta-galactosidase (Landing disease
and Morquito type B disease), beta-mannosidase (mannosidosis) and
alpha-L-iduronidase (Hurler-Scheie disease). Examination of known
3D structures from some families of the clan allowed us to deduce
structural and functional features shared by these proteins. We then
used the hydrophobic cluster analysis method to study the protein
sequences of the entire clan. Our results reveal that, despite low levels
of sequence identity, all the proteins of the clan (including the
aforementioned lysosomal enzymes) likely share a similar catalytic domain
consisting of an (alpha/beta)8 barrel with conserved functional amino
acids located at the C-terminal ends of six of the eight strands
constituting the beta-barrel. Interestingly, several mutations reported to
be responsible for lysosomal storage diseases are located within
these conserved regions of the lysosomal enzyme catalytic domains.
Webpage Link
