Isolation and characterization of Helothermine, a novel toxin from Heloderma horridum horridum (Mexican beaded lizard) venom

Mochca-Morales, Javier; Martin, Brian M.; Possani, Lourival D.

doi:10.1016/0041-0101(90)90065-f

Cited by 93 publications

(45 citation statements)

References 22 publications

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“…In contrast, the mouse CRISP-3 protein has been shown to be expressed in the male salivary gland [30] and in developing B-cells, where a possible lytic activity might be related to antimicrobial activity in saliva and in the blood or lymph [59]. Helothermine, a toxin with hypothermic effects originating from the salivary secretion of the Mexican beaded lizard, Heloderma horridum, has been found to be another member of the CRISP family [49,53]. Based on the finding that helothermine blocks the ryanodine receptor in striated muscle, the possibility was suggested that CRISP-like proteins may endogenously regulate ryanodine receptors in mammalian tissues.…”

Section: T  3 Homology Of Pr-1 Type Proteins From Plants and Othmentioning

confidence: 99%

The families of pathogenesis-related proteins, their activities, and comparative analysis of PR-1 type proteins

Loon

Strien

1999

Physiological and Molecular Plant Pathology

1,660

929

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Section: T  3 Homology Of Pr-1 Type Proteins From Plants and Othmentioning

confidence: 99%

The families of pathogenesis-related proteins, their activities, and comparative analysis of PR-1 type proteins

Loon

Strien

1999

Physiological and Molecular Plant Pathology

1,660

929

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“…Even the activities of forms that may play important roles, such as those with high expression levels in specific tissue or organs, remain unknown. The basal activity of the CRISP venom protein is likely to be relaxation of peripheral smooth muscle, such as helothermine from H. horridum (46), and may indicate a tissue-specific role for the ancestral normal body protein. The kallikrein toxins are an example of where an ancestral body action (liberation of bradykinin from kininogen) is preserved, but some toxin isoforms have derived additional activities (e.g.…”

Section: Evolution Of An Arsenalmentioning

confidence: 99%

Evolution of an Arsenal

Fry

Scheib²,

Weerd³

et al. 2008

Molecular & Cellular Proteomics

313

145

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Venom is a key innovation underlying the evolution of advanced snakes (Caenophidia). Despite this, very little is known about venom system structural diversification, toxin recruitment event timings, or toxin molecular evolution. A multidisciplinary approach was used to examine the diversification of the venom system and associated toxins across the full range of the ϳ100 million-year-old advanced snake clade with a particular emphasis upon families that have not secondarily evolved a front-fanged venom system (ϳ80% of the 2500 species). Analysis of cDNA libraries revealed complex venom transcriptomes containing multiple toxin types including three finger toxins, cobra venom factor, cysteine-rich secretory protein, hyaluronidase, kallikrein, kunitz, lectin, matrix metalloprotease, phospholipase A 2 , snake venom metalloprotease/a disintegrin and metalloprotease, and waprin. High levels of sequence diversity were observed, including mutations in structural and functional residues, changes in cysteine spacing, and major deletions/truncations. Morphological analysis comprising gross dissection, histology, and magnetic resonance imaging also demonstrated extensive modification of the venom system architecture in nonfront-fanged snakes in contrast to the conserved structure of the venom system within the independently evolved front-fanged elapid or viperid snakes. Further, a reduction in the size and complexity of the venom system was observed in species in which constriction has been secondarily evolved as the preferred method of prey capture or dietary preference has switched from live prey to eggs or to slugs/snails. Investigation of the timing of toxin recruitment events across the entire advanced snake radiation indicates that the evolution of advanced venom systems in three front-fanged lineages is associated with recruitment of new toxin types or explosive diversification of existing toxin types. These results support the role of venom as a key evolutionary innovation in the diversification of advanced snakes and identify a potential role for non-front-fanged venom toxins as a rich source for lead compounds for drug design and development.

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“…Among the PR proteins, Tex31 displays the highest sequence identity (36%) to a subfamily of PR proteins found in mammals and known as the cysteine-rich secretory proteins (CRISPs). Like the CRISP subfamily (24), which includes Tpx-1 (19) and helothermine (20), Tex31 possess a characteristic cysteine-rich Cterminal region, with 19 of its 22 cysteine residues found in the C terminus.…”

Section: Fig 3 Sequence Alignment Of Representative Pathogenesis-rementioning

confidence: 99%

“…Over sixty-five proteins with high sequence homology to the plant PR-1 family have now been identified in the animal (invertebrates and vertebrates, including humans) and fungal kingdoms. Proteins include the human brain tumor PR proteins GliPR (17) and RTVP-1 (18), mammalian Tpx-1, testis-specific protein (19), helothermine, from lizard venom (20), antigen 5 from Vespula vilgaris venom (21), and proteins from fungi (Saccharomyces, Schizophylum) (22). Sequence alignment of PR proteins reveals a highly conserved core of amino acids (Fig.…”

Section: Fig 3 Sequence Alignment Of Representative Pathogenesis-rementioning

confidence: 99%

Isolation and Characterization of a Cone Snail Protease with Homology to CRISP Proteins of the Pathogenesis-related Protein Superfamily

Milne

Abbenante

Tyndall

et al. 2003

Journal of Biological Chemistry

208

205

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The pathogenesis-related (PR) protein superfamily is widely distributed in the animal, plant, and fungal kingdoms and is implicated in human brain tumor growth and plant pathogenesis. The precise biological activity of PR proteins, however, has remained elusive. Here we report the characterization, cloning and structural homology modeling of Tex31 from the venom duct of Conus textile. Tex31 was isolated to >95% purity by activityguided fractionation using a para-nitroanilide substrate based on the putative cleavage site residues found in the propeptide precursor of conotoxin TxVIA. Tex31 requires four residues including a leucine N-terminal of the cleavage site for efficient substrate processing. The sequence of Tex31 was determined using two degenerate PCR primers designed from N-terminal and tryptic digest Edman sequences. A BLAST search revealed that Tex31 was a member of the PR protein superfamily and most closely related to the CRISP family of mammalian proteins that have a cysteine-rich C-terminal tail. A homology model constructed from two PR proteins revealed that the likely catalytic residues in Tex31 fall within a structurally conserved domain found in PR proteins. Thus, it is possible that other PR proteins may also be substrate-specific proteases.Of the genomes that have been completely sequenced, as many as 2% of the gene products encode known proteases, many of which regulate physiological processes such as blood coagulation, fibrinolysis, the complement system, and the processing of protein hormone precursors by specific convertases. Prohormones and neuropeptides (3-40 amino acids), important coordinators of cellular function in the endocrine and nervous systems, are often synthesized as propeptides. The propeptide is subsequently processed by substrate-specific proteases to yield the mature bioactive form (1). As many of the substratespecific proteases remain unidentified, predicting new bioactive peptides from cDNA sequences is presently difficult, if not impossible (2, 3). Linderström-Lang coined the term "limited proteolysis" to describe enzymes with restricted specificity (4). Enzyme activity can be restricted by substrate structure, enzyme processing state, endogenous protease inhibitor levels or a combination of these factors (5). Peptides derived from prohormones are typically flanked by a pair of dibasic residues (Lys-Arg, Arg-Arg, Lys-Lys, or Arg-Lys) and are cleaved by proteases found in secretory vesicles (1). However, many precursor peptides contain multiple sets of basic residues, suggesting that highly substrate specific or differentially expressed proteases can determine processing outcomes.The venom of cone snails (predatory marine molluscs of the genus Conus) has yielded a rich source of novel neuroactive peptides ("conotoxins") (6). However, the enzymes responsible for cleaving the conotoxins from their propeptide precursors have not been isolated. Here we report the purification, cloning, and initial characterization of Tex31, a protease from venom Conus textile. Interestingly,...

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Isolation and characterization of Helothermine, a novel toxin from Heloderma horridum horridum (Mexican beaded lizard) venom

Cited by 93 publications

References 22 publications

The families of pathogenesis-related proteins, their activities, and comparative analysis of PR-1 type proteins

The families of pathogenesis-related proteins, their activities, and comparative analysis of PR-1 type proteins

Evolution of an Arsenal

Isolation and Characterization of a Cone Snail Protease with Homology to CRISP Proteins of the Pathogenesis-related Protein Superfamily

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