| Abstract | This group of serine peptidases belong to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin)) and S53 (sedolisin) both of which are members of clan SB.
The subtilisin family is the second largest serine protease family characterised to date. Over 200 subtilises are presently known, more than 170 of which with their complete amino acid sequence [ 9070434]. It is widespread, being found in eubacteria,
archaebacteria, eukaryotes and viruses [7845208]. The vast majority of the family are endopeptidases, although there is an exopeptidase, tripeptidyl peptidase [7845208, 8439290]. Structures have been determined for several members of the subtilisin family: they exploit the same catalytic triad as the chymotrypsins, although the residues occur in a different order (HDS in
chymotrypsin and DHS in subtilisin), but the structures show no other
similarity [7845208, 8439290]. Some subtilisins are mosaic proteins, and others
contain N- and C-terminal extensions that show no sequence similarity to
any other known protein [7845208]. Based on sequence homology, a subdivision into six families has been proposed [9070434].
The proprotein-processing endopeptidases kexin, furin and related enzymes
form a distinct subfamily known as the kexin subfamily (S8B). These preferentially
cleave C-terminally to paired basic amino acids. Members of this subfamily
can be identified by subtly different motifs around the active site [7845208, 8439290].
Members of the kexin family, along with endopeptidases R, T and K from the
yeast Tritirachium and cuticle-degrading peptidase from Metarhizium, require
thiol activation. This can be attributed to the presence of Cys-173 near to
the active histidine [8439290].Only 1 viral member of the subtilisin family is known, a 56-kDa protease from herpes virus 1, which infects the channel catfish [7845208].
Sedolisins (serine-carboxyl peptidases) are proteolytic enzymes whose fold resembles that of subtilisin; however, they
are considerably larger, with the mature catalytic domains containing approximately 375 amino acids. The defining
features of these enzymes are a unique catalytic triad, Ser-Glu-Asp, as well as the presence of an aspartic acid
residue in the oxyanion hole. High-resolution crystal structures have now been solved for sedolisin from Pseudomonas
sp. 101, as well as for kumamolisin from a thermophilic bacterium, Bacillus novo sp. MN-32. Mutations in the human gene leads to a fatal neurodegenerative disease [12673349]. |
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