Biochemical characterization of the lizard toxin gilatoxin

Abstract

The Gila monster (genus Heloderma) is the only known lizard to produce and inject a venomous secretion. Little is known about the venom from these lizards, and none of the toxins have been isolated until this time. This paper reports the isolation and characterization of a major lethal toxin (gilatoxin) from the venoms of Heloderma suspectum and Heloderma horridum. Gilatoxins from both species were similar in amino acid composition, electrophoretic mobility, pI, and immunological reactivity. They are acidic proteins possessing molecular weights of 35 000-37 500 and isoelectric points of 4.25 and consist of a single polypeptide chain. Neither is antigenically related to the venoms of snakes. The toxins are devoid of phospholipase A2 activity and proteolytic, hemorrhagic, and hemolytic activities, with lethality being the only biological activity detectably expressed. The toxins appear to be unique and distinct from those of other venomous animals.

Blarina toxin, a mammalian lethal venom from the short-tailed shrew Blarina brevicauda : Isolation and characterization

“…However, the factors contributing to the lethality of snake venom are relatively small proteolytic degradation products with molecular sizes of 60-75 aa. Among lizard venoms, GTX and horridum toxin resemble mammal kallikreins with regard to their amino acid sequences and protease activities (16,(32)(33)(34). The LD 50 values of GTX and horridum toxin injected i.v.…”

Gila Monster Envenomation: A Review for the Emergency Medicine Physician

“…L-amino acid oxidase splits fibrinogen which can lead to platelet aggregation and phospholipase A2 cleaves lecithin to lysolecithin which can weaken cell membranes and allow for efficient spread of venom. 4,10 Gilatoxin, molecular weight 35,000, is a strongly antigenic toxin that has been shown to be a serine protease with kallikerkerin-like and thrombin-activating activity. 4,5 The gilatoxin may potentiate hypotension through the breakdown of angiotensin I and can lead to anaphylactoid reactions through its homology to other mammalian peptides.…”

Recent aspects of chemical ecology: Natural toxins, coral communities, and symbiotic relationships

“…Various kallikrein-type proteases have been identified in snake venom, e.g., ancrod (Calloselasma rhodostoma), batroxobin (Bothrops atrox), and crotalase (Crotalus adamanteus), but they are not lethal. With regard to lizard venoms, gila toxin (GTX) and horridum toxin (HTX) resemble mammalian kallikreins with regard to their amino acid sequences and protease activities [25,26]. The LD 50 values of GTX and HTX injected iv into mice are 2.5 mg/kg body weight [27], i.e., nearly equivalent to, or slightly higher than, that of BLTX.…”

“…Symbiodinolide has a 62-membered mono-sulfated macrolactone moiety, bis-epoxide moiety, 6,6-spiroacetal and hemiacetal rings. With the use of an excess amount of the second-generation Hoveyda-Grubbs' catalyst (25), symbiodinolide (15) has been successfully degraded to afford three fragments: C14-C23, C24-33, and C34-41 (20)(21)(22) (Fig. 16) [79].…”