Snake venoms are rich sources of metalloproteinases that are of biological interest due to their diverse molecular
diversity and selective therapeutic applications. Snake venoms metalloproteinases (SVMPs) belong to the MEROPS
peptidase family M12B or reprolysin subfamily, which are consisted of four major domains include a reprolysin catalytic
domain, a disintegrin domain, a reprolysin family propeptide domain and a cysteine-rich domain. The appropriate structural
and massive sequences information have been available for SVMPs family of enzymes in the Protein Data Bank and
National Center for Biotechnology Information, respectively. Functional essentiality of every domain and a crucial contribution
of binding geometry, primary specificity site, and structural motifs have been studied in details, pointing the way
for designing potential anti-coagulation, antitumor, anti-complementary and anti-inflammatory drugs or peptides. These
enzymes have been reported to degrade fibrinogen, fibrin and collagens, and to prevent progression of clot formation. Angiotensin-
converting enzyme activity, antibacterial properties, haemorrhagic activity and platelet aggregation response of
SVMPs have been studied earlier. Structural information of these enzymes together with recombinant DNA technology
would strongly promote the construction of many recombinant therapeutic peptides, particularly fibrinogenases and vaccines.
We have comprehensively reviewed the structure-function-evolution relationships of SVMPs family proteins and
their advances in the promising target models for structure-based inhibitors and peptides design. Moreover, structurefunction-
evolution integrity of metalloproteinase from Gloydius halys venom was preliminarily analyzed herein that may
provide a conceptual idea for the future of antibacterial peptide design.