Proteolytic venoms

Januario AH, Simone LS, Silvana M, et al. Neo-clerodane diterpenoid, a new metallo-protease snake venom inhibitor from Baccharis trimera (Asteraceae) anti-proteolytic and anti-hemorrhagic properties. Chem Biol Interact 2002 150 243-251. 

In addition to the proposed regulatory role of ATP and pyrophosphate, some possibility exists that 3, 5 -cyclic phosphate diesterase is under physiological control. Such ideas arose through observations of Cheung (43, 62) that the partially purified enzyme from beef brain was markedly activated by snake venom. The stimulatory factor was labile at extreme pH it was not dialyzable and appeared to be a protein. A similar activating factor is also present in brain tissue (63) and is removed during purification of the diesterase. It seems to interact stoichiometrically with the enzyme. The activator is destroyed by trypsin and is not proteolytic itself. The precise role of this protein in regulating the phosphodiesterase in vivo is not yet established, however. 

The role of zinc in the enzymes listed in Table 12 is very often that of a strong Lewis acid, in which substrates are coordinated, polarized and hence activated. In other cases, zinc may play a regulatory, structural or template role. Zinc may also have a structural function in other biological molecules, for example in the unwinding and subsequent rewinding of the double-stranded polymers involved in replication and transcriptional processes. There is also evidence for a role for zinc in the stabilization of membranes and cell walls.463 The high concentrations of zinc in certain snake venoms reflect the presence in the venom of proteolytic enzymes and hemorrhagic toxins that all require zinc for activity.464... 

TOXINS are taken here to be substances that have a deleterious action on another organism, and archetypal toxins were originally of natural origin. This classification is necessarily somewhat discretionary, and toxins with a predominant action on neurons are grouped under another heading see NEUROTOXINS. Toxins may be used defensively (bitter and poisonous alkaloids in skin or leaves), or offensively (venoms injected or administered to the prey by means of specialized apparatus), or are the proteolytic enzymes elaborated by infecting parasites. Some typical or... 

Finally, an outstanding example of research into marine bioactive peptides is that of the conotoxin peptides derived from the venom of marine snails of the genus Conus [159]. The initial propeptide is processed by both post-translational modification and proteolytic cleavage into a variety of small peptides which are 10-50 amino acids in length [160, 161]. Research into potential therapeutic applications of the conotoxins has shown that a number of these peptides interact uniquely with ion channels to induce a wide variety of pharmacological effects in mammalian systems [162-164]. General reviews of the conotoxins are available [160, 165], as well as more-detailed reviews of their structures [166] and potential therapeutic uses [166-168]. 

The mammalian pancreatic enzymes (group IB) have primarily a digestive role and are secreted as the pro-enzyme (zymogen) that requires subsequent proteolytic cleavage to remove a hexapeptide at the N-terminus. The pro-enzyme is unable to bind to the phospholipid interface. Unlike the cobra venom enzyme, the pancreatic enzyme expresses low activity with a zwitterionic interface such as that provided by phosphatidylcholine. The enzyme has a considerable preference for an anionic interface that can be provided by anionic phospholipid per se or by the inclusion of other anionic lipids in the... 

Zinc is also found in purified hemorrhagic toxins and proteolytic enzymes from venoms. Fibrinogenase is a proteolytic enzyme which renders fibrinogen unclottable. This has one Zn per molecule of protein. Further examples include a peptidase from the venom of Agkistrodon... 

The proteolytic release of M. from promelittin probably occurs outside the venom gland cells. Since M. disrupts phospholipid membranes, it is not surprising that the promelittin inside the secretory cells is... 

Spider toxins toxic substances produced in the venom glands of many spiders. They serve to paralyse and kill prey, and are dangerous to humans only in rare cases, e.g. the toxin of the South European La-trodectus tredecimgutlatus, or the American black widow (Latrodectus mactans). The active principles of S.t. are proteinaceous and related to those of snake and scorpion venoms. They contain hyaluronidase and proteolytic activity, but phospholipases and hemolytic or blood clotting activities are absent. 

Dextran induced the synthesis of a dextranase, which is attached to the outer membrane of the envelope, by an aerobic. Gram-negative bacterium closely related to Cytophaga Johnsonii. The use of proteolytic enzymes, snake venoms, and detergents in solubilizing a dextranase from C.johnsonii has been examined. Chymotrypsin was the only protease that efficiently solubilized the enzyme without destroying the enzymic activity. 

In nature, the art of chemical warfare may have reached its zenith with the innovation of venomous animals, those that not only contain poisonous toxins but also have the anatomical apparatus to inject those toxins directly into other animals. Venoms come in four different types cytotoxic, causing cell death proteolytic, dismantling the molecular structure around the area of the injection hemotoxic, causing failure within the cardiovascular system or neurotoxic, acting on the nervous system and the brain. 

E. Proteolytic Enzymes. Certain snake venoms are rich in proteolytic enzymes, especially those of Crotalidae and Viperidae, which have strong endopeptidases. Elapidae venoms usually do not contain endopeptidase but are rich in di- and tripeptidases. Some snake venoms contain very specific proteases, cleaving only specific peptide bonds. 

E. Fibrinolytic Enzymes. Some snake venom proteolytic enzymes can dissolve blood clots, fibrin, without causing hemorrhage. Unlike tissue plasminogen activator (tPA) which liberates plasmin from plasminogen, venom fibrinolytic enzymes hydrolyze fibrin directly. These enzymes have potential therapeutic use in dissolving thrombi. Many such enzymes have been isolated (Retzios and Markland, 1988 Willis and Tu, 1988 Siigur and Siigur, 1991). 

Figure 3. Alignment of proteolytically derived peptides from Solenopsis invicta venom phospholipase (76) with Dolichovespula maculata venom phospholipase isozyme 1 (69). The double dots indicate identical residues and the single dots residues that differ by only a single base (conservative substitutions). Dashes indicate positions inserted to maximize alignment.

The venoms of fire ants of the genus Solenopsis also contain a phospholipase, e.g. Sol i 1 (13,74,75). This phospholipase is immunologically cross-reactive with vespid venom phospholipases. Although the complete amino acid sequences of fire ant phospholipases have not been reported, the sequences of a number of proteolytic fragments are known and clearly establish that Sol i 1 and Sol r 1 are members of the same protein family as vespid venom phospholipase (76) (Fig. 3). 

Acid phosphatase is found in bee venoms as a dimer of a protein chain of about 49000 molecular weight (61, 98, 99, 100, 101, 102). Acid phosphatase activity cannot be consistently demonstrated in venoms from vespid wasps. The N-terminal sequence and the sequences of a number of proteolytic peptides from honeybee venom acid phosphatase have recently been reported (103). The venom acid phosphatase is more closely related to mammalian prostatic type acid phosphatases (104, 105, 106, 107, 108) than to lysosomal type acid phosphatases (109, 110), as is illustrated in Fig. 5. 

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