The Sequence and Three-Dimensional Structure Characterization of Snake Venom Phospholipases B

Area of Science:

• Biochemistry
• Structural Biology
• Toxicology

Background:

• Snake venom phospholipases B (SVPLBs) are the most potent hemolytic agents in snake venom, yet remain understudied.
• No prior structural information exists for SVPLBs, hindering understanding of their role in envenomation.

Purpose of the Study:

• To generate the first model-based 3D structure of Bothrops moojeni phospholipase B (PLB_Bm).
• To analyze the structural features of PLB_Bm and compare it with homologous enzymes.
• To provide insights into the structure-function relationship and envenomation mechanisms of SVPLBs.

Main Methods:

• Homology modeling using I-TESSER, MODELLER 9v19, and Swiss-Model.
• Structural validation employing PROCHECK, ERRAT, and Verif3D.
• Sequence and structural comparisons with other phospholipases B.

Main Results:

• A 491-residue model for PLB_Bm was generated, featuring an αββα sandwich core and Ntn-hydrolase fold.
• The mature PLB_Bm structure consists of two chains (A: 207 residues, B: 266 residues).
• Comparisons revealed variations in length, sequence, surface charge, and active site cavity among different PLBs, suggesting altered substrate specificities.

Conclusions:

• The modeled structure of PLB_Bm provides a foundation for understanding SVPLB function.
• Structural differences among PLBs may explain variations in hemolytic activity and substrate specificity.
• This study enhances knowledge of SVPLB structure-function relationships in snakebite envenomation.