Lg. Jia et al., SNAKE-VENOM METALLOPROTEINASES - STRUCTURE, FUNCTION AND RELATIONSHIPTO THE ADAMS FAMILY OF PROTEINS, Toxicon, 34(11-12), 1996, pp. 1269-1276
A large number of zinc metalloproteinases of varying mel. wts and biol
ogical functions has been isolated from crotalid and viperid venoms. O
ver the past few years, structural studies on these proteinases have s
uggested their organization into four classes, P-I to P-IV. These prot
einases are synthesized in the venom gland as zymogens which are subse
quently processed to the active form. The signal and pro-sequences of
the proteins are highly conserved. Within the pro-domain lies a consen
sus sequence which probably functions in a manner similar to the cyste
ine switch in mammalian collagenases. The proteinase domain is represe
nted by two forms: a two-disulfide and a three-disulfide structure. Cr
ystallographic and modeling studies suggest that the two forms share v
ery similar tertiary structures. The larger venom metalloproteinases (
P-II, III and IV) have additional domains on the carboxy side of the p
roteinase domain. The additional domains that have been identified inc
lude disintegrin and disintegrin-like domains, a high-cysteine domain
and a lectin-binding domain. It appears that these non-enzymatic domai
ns function to modulate the biological properties of the proteinases.
Recently, a family of homologues of the venom zinc metalloproteinases
has been described from a variety of organisms including mammals, rept
iles and invertebrates. This family of proteins has been termed the AD
AMs, for A Disintegrin-like And Metalloproteinase-containing protein.
They differ from the venom proteinases in that some of them may not ha
ve proteolytic activity. In addition to the domain structure described
for the P-III class of venom proteins, the ADAMs have an epidermal gr
owth factor-like domain, a transmembrane domain and a cytoplasmic doma
in. A description of venom metalloproteinase structure will be outline
d in this review, along with the similarities and differences among th
e venom proteins and the ADAMs family of proteins. Copyright (C) 1996
Elsevier Science Ltd