Snake venom metalloproteinases

Area of Science:

• Biochemistry
• Toxicology
• Proteomics

Background:

• Metalloproteinases are major components in Crotalid and Viperid snake venoms.
• Snake venom metalloproteinases (SVMPs) possess a wide array of biological activities.
• Understanding SVMP structure is crucial for elucidating their diverse functions.

Purpose of the Study:

• To discuss the multiple activities of snake venom metalloproteinases (SVMPs).
• To review the structural classification and variations within the SVMP family.
• To highlight advances in understanding SVMP structure and active site.

Main Methods:

• Review of proteomic analyses of snake venoms.
• Analysis of literature on SVMP activities and structural classifications.
• Examination of crystal structures of SVMPs, including P-I and P-III classes.

Main Results:

• SVMPs display diverse activities: hemorrhagic, fibrin(ogen)olytic, prothrombin activation, Factor X activation, apoptosis induction, platelet aggregation inhibition, pro-inflammation, and serine proteinase inhibitor inactivation.
• SVMPs are classified into P-I, P-II, and P-III classes based on size and domain structure (pro, proteinase, disintegrin, cysteine-rich).
• Crystal structures reveal the active site's consensus HEXXHXXGXXHD sequence and a unique 'Met-turn' stabilizing zinc-binding histidines.

Conclusions:

• SVMPs possess multifaceted roles in envenomation beyond simple tissue degradation.
• Structural diversity of SVMPs correlates with their varied biological functions.
• Detailed structural information, particularly of the active site, advances our understanding of SVMP mechanisms.