Mapping the structural determinants of presynaptic neurotoxicity of snake venom phospholipases A2

Abstract: Phospholipases A2 enzymes are found in many mammalian tissues and in animal venoms. Those present in bee venom (bvPLA2) and snake venom (svPLA2) have been studied more particularly for their biological activities of interest. Although they belong to the same family of secreted PLA2 (sPLA2), bvPLA2 and svPLA2 differ from a structural and functional point of view. In this review, we describe the morphological characteristics of these two enzymes and the structural determinants that govern their functions. After describing their cytotoxicity, we compared their biological activities, including antimicrobial, anti-tumor, anti-inflammatory, anti-neurodegenerative, and anti-nociceptive effects. In addition, we highlighted their therapeutical applications and deduced bvPLA2 has better potential than svPLA2 in biotechnological and pharmaceutical innovations.

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Mapping structural determinants of biological activities in snake venom phospholipases A2 by sequence analysis and site directed mutagenesis

Toxicon ◽

10.1016/j.toxicon.2003.11.027 ◽

2003 ◽

Vol 42 (8) ◽

pp. 869-883 ◽

Cited By ~ 61

Author(s):

Lucimara Chioato ◽

Richard J Ward

Keyword(s):

Sequence Analysis ◽

Snake Venom ◽

Biological Activities ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Structural Determinants ◽

Phospholipases A2

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Characterization of Venoms of Deinagkistrodon acutus and Bungarus multicinctus Using Proteomics and Peptidomics

Current Proteomics ◽

10.2174/1570164617666191121112319 ◽

2020 ◽

Vol 17 (3) ◽

pp. 241-254

Author(s):

Yaqiong Zhang ◽

Zhiping Jia ◽

Yunyang Liu ◽

Xinwen Zhou ◽

Yi Kong

Keyword(s):

Snake Venom ◽

Protein Families ◽

Traditional Medicines ◽

Phospholipases A2 ◽

Inhibitory Peptides ◽

Sds Page ◽

Deinagkistrodon Acutus ◽

Venom Proteins ◽

Proteins And Peptides

Background: Deinagkistrodon acutus (D. acutus) and Bungarus multicinctus (B. multicinctus) as traditional medicines have been used for hundreds of years in China. The venoms of these two species have strong toxicity on the victims. Objective: The objective of this study is to reveal the profile of venom proteins and peptides of D. acutus and B. multicinctus. Method: Ultrafiltration, SDS-PAGE coupled with in-gel tryptic digestion and Liquid Chromatography- Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS/MS) were used to characterize proteins and peptides of venoms of D. acutus and B. multicinctus. Results: In the D. acutus venom, 67 proteins (16 protein families) were identified, and snake venom metalloproteinases (SVMPs, 38.0%) and snake venom C-type lectins (snaclecs, 36.7%) were dominated proteins. In the B. multicinctus venom, 47 proteins (15 protein families) were identified, and three-finger toxins (3FTxs, 36.3%) and Kunitz-type Serine Protease Inhibitors (KSPIs, 32.8%) were major components. In addition, both venoms contained small amounts of other proteins, such as Snake Venom Serine Proteinases (SVSPs), Phospholipases A2 (PLA2s), Cysteine-Rich Secreted Proteins (CRISPs), 5'nucleotidases (5'NUCs), Phospholipases B (PLBs), Phosphodiesterases (PDEs), Phospholipase A2 Inhibitors (PLIs), Dipeptidyl Peptidases IV (DPP IVs), L-amino Acid Oxidases (LAAOs) and Angiotensin-Converting Enzymes (ACEs). Each venom also had its unique proteins, Nerve Growth Factors (NGFs) and Hyaluronidases (HYs) in D. acutus, and Cobra Venom Factors (CVFs) in B. multicinctus. In the peptidomics, 1543 and 250 peptides were identified in the venoms of D. acutus and B. multicinctus, respectively. Some peptides showed high similarity with neuropeptides, ACE inhibitory peptides, Bradykinin- Potentiating Peptides (BPPs), LAAOs and movement related peptides. Conclusion: Characterization of venom proteins and peptides of D. acutus and B. multicinctus will be helpful for the treatment of envenomation and drug discovery.

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Short Linear Motifs Characterizing Snake Venom and Mammalian Phospholipases A2

Toxins ◽

10.3390/toxins13040290 ◽

2021 ◽

Vol 13 (4) ◽

pp. 290

Author(s):

Caterina Peggion ◽

Fiorella Tonello

Keyword(s):

Snake Venom ◽

Protein Interactions ◽

Biological Properties ◽

Protein Protein Interactions ◽

Sequence Alignments ◽

Toxic Activity ◽

Short Linear Motifs ◽

Phospholipases A2 ◽

Group I ◽

Linear Motifs

Snake venom phospholipases A2 (PLA2s) have sequences and structures very similar to those of mammalian group I and II secretory PLA2s, but they possess many toxic properties, ranging from the inhibition of coagulation to the blockage of nerve transmission, and the induction of muscle necrosis. The biological properties of these proteins are not only due to their enzymatic activity, but also to protein–protein interactions which are still unidentified. Here, we compare sequence alignments of snake venom and mammalian PLA2s, grouped according to their structure and biological activity, looking for differences that can justify their different behavior. This bioinformatics analysis has evidenced three distinct regions, two central and one C-terminal, having amino acid compositions that distinguish the different categories of PLA2s. In these regions, we identified short linear motifs (SLiMs), peptide modules involved in protein–protein interactions, conserved in mammalian and not in snake venom PLA2s, or vice versa. The different content in the SLiMs of snake venom with respect to mammalian PLA2s may result in the formation of protein membrane complexes having a toxic activity, or in the formation of complexes whose activity cannot be blocked due to the lack of switches in the toxic PLA2s, as the motif recognized by the prolyl isomerase Pin1.

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