Biomedical Engineering Reference
In-Depth Information
Figure 2.1
Metzincins. The classification of metalloendopeptidases is based on their
zinc-binding motif. The amino acids are displayed in the one letter code,
and X denotes flexible residues. The metzincins, belonging to the zincins,
contain the additional Met-turn, a conserved motif, responsible for
enhanced thermal stability of the enzymes. Meprin a and b are two out of
seven members of human astacins. The graphic is based on Gomis-Ru
ยจ
th.
5
BMP-1: bone morphogenetic protein-1; Hsa: Homo sapiens; mTld:
mammalian tolloids; Tll-1 and Tll-2: tolloid like-1 and -2.
tetrahedral transition state intermediate, which is further stabilized by the zinc
and by a tyrosine residue from the Met-turn. Finally, breakdown of this
intermediate is facilitated by protonation of the leaving amine.
There are three major groups of metzincins found in humans (Figure 2.1): the
matrix metallo-proteinases (MMPs) often involved in ECM degradation and
tumor proliferation, the adamalysins, including the ADAMs (a disintegrin and
metalloproteases domain) responsible for many proteolytic shedding events at
the cell surface, and finally the astacins.
5,9-11
In humans, seven different astacin proteases exist: meprin a and b, BMP-1
(bone morphogenetic protein-1) and mTld (mammalian tolloids), Tll-1 and Tll-2
(tolloid like-1 and -2), and ovastacin. These enzymes all share the astacin-typical
catalytic domain but exhibit unique features regarding their exosite regions.
1,5
BMP-1 and the tolloids have been shown to be crucial players in collagen
fibril assembly and dorsal/ventral patterning during embryogenesis.
12-15
Ovastacin is expressed in early oocytes and might be important for the hatching
of the embryo, as is known for many other astacin proteases from different
species.
16-18
However, the latest proteomics datasets revealed a broader dis-
tribution of ovastacin (http://www.ebi.ac.uk/pride/simpleSearch.do), indicating
other biological activities.
