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

Abstract

Snake venom phospholipases B (SVPLBs) are the least studied enzymes. They constitute about 1% of Bothrops crude venoms, however, in other snake venoms, it is present in less than 1%. These enzymes are considered the most potent hemolytic agent in the venom. Currently, no structural information is available about these enzymes from snake venom. To better understand its three-dimensional structure and mechanisms of envenomation, the current work describes the first model-based structure report of this enzyme from Bothrops moojeni venom named as B. moojeni phospholipase B (PLB_Bm). The structure model of PLB_Bm was generated using model building software like I-TESSER, MODELLER 9v19, and Swiss-Model. The build PLB_Bm model was validated using validation tools (PROCHECK, ERRAT, and Verif3D). The analysis of the PLB_Bm modeled structure indicates that it contains 491 amino acid residues that form a well-defined four-layer αββα sandwich core and has a typical fold of the N-terminal nucleophile aminohydrolase (Ntn-hydrolase). The overall structure of PLB_Bm contains 18 β-strands and 17 α-helices with many connecting loops. The structure divides into two chains (A and B) after maturation. The A chain is smaller and contains 207 amino acid residues, whereas the B chain is larger and contains 266 amino acid residues. The sequence and structural comparison among homologous snake venom, bacterial, and mammals PLBs indicate that differences in the length and sequence composition may confer variable substrate specificity to these enzymes. Moreover, the surface charge distribution, average volume, and depth of the active site cavity also vary in these enzymes. The present work will provide more information about the structure-function relationship and mechanism of action of these enzymes in snakebite envenomation.

A current perspective on snake venom composition and constituent protein families

“…This protein family was present in 30% of species and had a mean abundance of 0.5% and a maximum of 3%. They have a molecular mass of 35 to 55 kDa (Bernheimer et al 1987;Ullah and Masood 2020). There have been limited investigations into this protein family, and their function and role in human envenomation is unclear.…”

Inhibition of SARS-CoV-2 3CL Mpro by Natural and Synthetic Inhibitors: Potential Implication for Vaccine Production Against COVID-19

“…The MDMoby and MDweb programs (Hospital et al, 2012), GROMACS (Berendsen et al, 1995), AMBER16 (Case et al, 2005;Maier et al, 2015) were used for Molecular Dynamic Simulation as described previously (Ullah et al, 2019;Ullah and Masood, 2020). The all-atom-protein interaction was found out using FF14SB force field (Darden et al, 1993).…”

Evaluation of the effects of Loxosceles intermedia’s venom in zebrafish

“…Such studies have shown that the presence and abundance of certain phospholipids in the cell membrane composition could be responsible for increased sensitivity to lysis [22] , [42] . This might be associated to the differential preferences that Phospholipases D (PLDs) exhibit for phospholipid targets [25] , [43] . Upon substrate cleavage, phospholipases produce membrane injury and consequently, provoke the remodelling of the membrane structure [44] , lipid raft formation [45] , and produce inflammatory mediators responsible for cell recruitment, cell death and fibrosis [3] .…”