Relationship between catalysis and toxicological properties of three phospholipases A2 from elapid snake venoms

Fletcher, Jeffrey E.; Rapuano, Bruce E.; Condrea, Eleonora; Yang, Chen-Chung; Rosenberg, Philïp

doi:10.1016/0041-008x(81)90209-x

Cited by 78 publications

(20 citation statements)

References 27 publications

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“…were observed in cat, human and horse erythrocytes, followed by rabbit, rat, and finally dog erythrocytes. While these results partially agree with previous reports (7,8,11,14,16,22), they differ in regard to relative sensitivities. Condrea et al (9) found that guinea pig and dog erythrocytes were more sensitive to the hemolityc action of…”

Section: Resultssupporting

confidence: 37%

Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

Troiano¹,

Gould²,

Gould³

2006

J. Venom. Anim. Toxins incl. Trop. Dis

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ABSTRACT:A comparative study on the sensitivity of erythrocytes from different vertebrate species (avian, mammalian and reptilian) to the hemolytic action caused by cardiotoxin isolated from Naja naja atra venom was carried out. Cardiotoxin was able to induce direct hemolysis in washed erythrocytes from several animals, except for llama. The EC50 values from hemolysis of the most sensitive (cat) and the most resistant (snake) animal varied approximately tenfold. According to the cell behavior, it was possible to characterize four types of behavior: The first was observed in cat, horse and human cells; the second in rat, rabbit and dog erythrocytes; and the third only in llama erythrocytes, which were resistant to cardiotoxin concentrations up to 300 µg/ml. Finally, avian and reptilian erythrocytes were more resistant to cardiotoxin III-induced hemolysis than those of the mammalian species.

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Section: Resultssupporting

confidence: 37%

Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

Troiano¹,

Gould²,

Gould³

2006

J. Venom. Anim. Toxins incl. Trop. Dis

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“…The lysophospholipids on the other hand are involved in cell signaling and phospholipid remodeling and are associated with membrane perturbation (9,10). Some members of the PLA 2 superfamily also present a wide variety of pharmacological effects, such as pre-and post-synaptic neurotoxicity (11,12), myotoxicity (13)(14)(15)(16)(17)(18)(19), cardiotoxicity (20), and platelet aggregation (21,22) among others.…”

mentioning

confidence: 99%

A Molecular Mechanism for Lys49-Phospholipase A2 Activity Based on Ligand-induced Conformational Change

Ambrósio

Nonato²,

Araújo

et al. 2005

Journal of Biological Chemistry

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Agkistrodon contortrix laticinctus myotoxin is a Lys49 -phospholipase A 2 (EC 3.1.1.4) isolated from the venom of the serpent A. contortrix laticinctus (broad-banded copperhead). We present here three monomeric crystal structures of the myotoxin, obtained under different crystallization conditions. The three forms present notable structural differences and reveal that the presence of a ligand in the active site (naturally presumed to be a fatty acid) induces the exposure of a hydrophobic surface (the hydrophobic knuckle) toward the C terminus. The knuckle in A. contortrix laticinctus myotoxin involves the side chains of Phe 121 and Phe 124 and is a consequence of the formation of a canonical structure for the main chain within the region of residues 118 -125. Comparison with other Lys49 -phospholipase A 2 myotoxins shows that although the knuckle is a generic structural motif common to all members of the family, it is not readily recognizable by simple sequence analyses. An activation mechanism is proposed that relates fatty acid retention at the active site to conformational changes within the C-terminal region, a part of the molecule that has long been associated with Ca 2؉ -independent membrane damaging activity and myotoxicity. This provides, for the first time, a direct structural connection between the phospholipase "active site" and the C-terminal "myotoxic site," justifying the otherwise enigmatic conservation of the residues of the former in supposedly catalytically inactive molecules.

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“…In addition, the relationship between hemolysis of red blood cells promoted by two typical snake venom CTXs and one abnormally large CTX is cnmpared to the hydrolysis of membrane bound phospholipids by these toxins to determine if PLA activity is crucial to the mechanism of red blood cell hemolysis. Since Sr 2 * is known to be as effe-tive as Ca 2 ÷ in supporting CTX contractures in skeletal muscle (Fletcher et al, 1981;Fletcher and Lizzo, 1987) and yet less effective than Ca 2 * in supporting PLA2 activity (Iwanaga and Suzuki, 1979), the effects of these two divalent cations on red blood cell hemolysis and phospholipid hydrolysis induced by the CTXs are contrasted.…”

Section: Rationalementioning

confidence: 99%

“…Phospholipids were analyzed by the method of BArtlett (1959), as previously described (Fletcher et al, 1981;1982;1990b).…”

Section: Gas Chromatographic Analysis Of Fatty Acids and Phospholipidsmentioning

confidence: 99%

Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A

Fletcher¹

1990

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Relationship between catalysis and toxicological properties of three phospholipases A2 from elapid snake venoms

Cited by 78 publications

References 27 publications

Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

A Molecular Mechanism for Lys49-Phospholipase A2 Activity Based on Ligand-induced Conformational Change

Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A

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