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.
Highlights
Phospholipases B (PLBs) or lysophospholipases (EC3.1.1.5) are high-molecular-mass enzymes that break ester linkages of glycerophospholipids of membranes at both positions sn-1 and sn-2 (Shiloah et al, 1973; Rokyta et al, 2011; Chapeaurouge et al, 2015). These enzymes have been named as PLBs (Doery and Pearson, 1964), phospholipase B-like (Doery and Pearson, 1964; Aird et al, 2013), Snake Venom Phospholipases B
The hemolytic activity of these enzymes is related to the hydrolysis of phosphatidylcholine (Bernheimer et al, 1986)
The primary structure of snake venom PLBs (SVPLBs) contains 553 amino acids in which the first 36 amino acids form the signal peptides and the remaining 526 make the PLB domain (Rokyta et al, 2011). Both monomeric and dimeric forms of PLBs have been reported to exist in snake venoms (Bernheimer et al, 1987; Chatrath et al, 2011)
Summary
Phospholipases B (PLBs) or lysophospholipases (EC3.1.1.5) are high-molecular-mass enzymes that break ester linkages of glycerophospholipids of membranes at both positions sn-1 and sn-2 (Shiloah et al, 1973; Rokyta et al, 2011; Chapeaurouge et al, 2015). The primary structure of SVPLB contains 553 amino acids in which the first 36 amino acids form the signal peptides and the remaining 526 make the PLB domain (Rokyta et al, 2011) Both monomeric and dimeric forms of PLBs have been reported to exist in snake venoms (Bernheimer et al, 1987; Chatrath et al, 2011). This free cysteine functions as one of the main amino acids in the active site of these enzymes, and they are called cysteine proteinases (Verma et al, 2016) This cysteine residue is fully conserved in all SVPLBs and PLBs of cow and mouse (Figure 1). The atomic coordinates of phospholipase B-like protein 1 from Bos taurus (PDB ID: 4BWC; 70% amino acid sequence identity with PLB_Bm) (Repo et al, 2014), were applied as a template
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