Venom enzymes hydrolyzing phosphate

Fig. 2). The staphylococcal enzyme may appear to be more akin in its mode of action to the spleen enzyme because they both hydrolyze DNA and RNA to 3 -nucleotides, whereas the venom enzyme releases 5 -nucleotides. However, their mode of action and specificity are quite different, and the structural requirements of the staphylococcal enzyme substrates are perhaps more nearly similar to those of the venom enzyme. The principal difference is that the staphylococcal enzyme cleaves the diester bond between the phosphate and the 5 -carbon of the sugar, whereas the venom enzyme cleaves on the other side of the phosphate, that is, between the phosphate and the nonspecific hydroxylic component of the diester bond. In contrast to both spleen and venom diesterases, the primary product released by staphylococcal nuclease hydrolysis is a derivative bearing a hydroxyl group (on the 5 position) rather than a phosphoryl group. Therefore, the 3 -phosphoryl product formed from polynucleotide hydrolysis is a secondary consequence of such cleavage. 

V. Other Venom Enzymes That Hydrolyze Phosphate Esters. . 328... 

The ATPase of most biological systems hydrolyzes the a-phosphate producing ADP + Pj. When ATP is used as a substrate, snake venom exonuclease hydrolyzes it to AMP and PP (pyrophosphate). However, when ATP is mixed with snake venom, it is hydrolyzed to adenosine, Pj and PP because snake venom contains an additional enzyme, 5 -nucleotidase. This can be summarized as follows ... 

The venom of poisonous snakes contains a class of enzymes known as phospholipases. These enzymes catalyze the breakdown of phospholipids, triglycerides in which one fatty acid has been replaced by a phosphate group. The venom of the eastern dia-mondback rattlesnake contains a phospholipase that hydrolyzes the ester bond at the middle carbon of phospholipids, if the larger of the two breakdown products of this reaction gets into the bloodstream, it dissolves the membranes of red blood cells, causing them to rupture. A bite from the eastern diamondback can lead to death if not treated immediately. 

Venom Phosphodiesterase. A phosphodiesterase from the venom of several species of snakes exhibits extreme specificity with regard to nucleotides. It hydrolyzes only components from a phosphate esterified at a 5 position. Thus, 5 nucleotides are liberated from RNA. The venom diesterase attacks both purine and pyrimidine nucleotides (Fig. 26). This activity was useful in establishing that 3 -5 linkages, rather than 2 -3 linkages, occur in nucleic acids. A similar enzyme occurs in intestines. 

Specific Phosphomonoesterase. A specific phosphomonoesterase that can be found commonly in snake venoms is 5 -nucleotidase, which hydrolyzes a variety of 5 -nucleotide phosphates. Thus the enzyme does not hydrolyze 2 - or 3 -phosphates of a guanosine, adenosine, cytidine, uridine, or adenosine 2 ,3 -cyclic phosphates. Nucleoside diphosphates of triphosphates are also not hydrolyzed by 5 -nucleotidase. 

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