Toxicity domain in presynaptically toxic phospholipase A2 of snake venom.
About 42 complete amino-acid sequences of phospholipases A2 (phosphatidylcholine 2-acylhydrolase, EC 3.1.1.4) are known, including those of 13 presynaptically toxic enzymes, but the structural features responsible for the neurotoxicity and distinguishing the toxins from the non-neurotoxic enzymes are far from being clear. In this study, we examined the charged-residue distributions and hydrophobic characteristics based on the sequence data and the predicted tertiary structure and proposed a possible toxicity domain. We found that the presynaptically toxic enzymes have three or four more basic amino-acid residues than the non-neurotoxic enzymes at positions 59, 60, 65, 70-73 and 97 or 98. These residues appear to cluster near the surface region at the N-terminal side. The cationic nature of this basic cluster in the toxin is enhanced by the alpha-amino group of the N-terminus and the dipole moment of helices 96-110 and 1-10. Moreover, these toxic-site residues are usually associated with hydrophobic regions at 1-7, 64-81 and 97-109.
Tsai
I H
IH
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, China.
Liu
H C
HC
Chang
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009420:Nervous System / Q000187:drug effects; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011487:Protein Conformation; D012910:Snake Venoms / Q000032:analysis / Q000633:toxicity*; D013329:Structure-Activity Relationship
D012910:Snake Venoms; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2