Isolation and characterization of DM40 and DM43, two snake venom metalloproteinase inhibitors from Didelphis marsupialis serum

Neves-Ferreira, Ana Gisele C.; Cardinale, Norma; Rocha, Surza Lucia Gonçalves da; Perales, Jonás; Domont, Gilberto B.

doi:10.1016/s0304-4165(00)00022-2

Cited by 57 publications

(105 citation statements)

References 45 publications

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“…Although some of the compounds showed a degree of neutralizing activity, none reached 100% protection (55 Numerous investigations are designed to understand the innate resistance of some animals to snake venoms. Some compounds have been isolated from snakes, opposums and other animals with promising results (56)(57)(58)(59)(60). However, the use of substances other than immunoglobulins may not guarantee the absence of anaphylactic reactions.…”

Section: Reaction)mentioning

confidence: 99%

Snake antivenoms: adverse reactions and production technology

Morais¹,

Massaldi²

2009

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

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Antivenoms have been widely used for more than a century for treating snakebites and other accidents with poisonous animals. Despite their efficacy, the use of heterologous antivenoms involves the possibility of adverse reactions due to activation of the immune system. In this paper, alternatives for antivenom production already in use were evaluated in light of their ability to minimize the occurrence of adverse reactions. These effects were classified according to their molecular mechanism as: anaphylactic reactions mediated by IgE, anaphylactoid reactions caused by complement system activation, and pyrogenic reactions produced mainly by the presence of endotoxins in the final product. In the future, antivenoms may be replaced by humanized antibodies, specific neutralizing compounds or vaccination. Meanwhile, improvements in antivenom quality will be focused on the obtainment of a more purified and specific product in compliance with good manufacturing practices and at an affordable cost.

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Section: Reaction)mentioning

confidence: 99%

Snake antivenoms: adverse reactions and production technology

Morais¹,

Massaldi²

2009

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

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“…Finally, we were interested in whether orthologs of Didelphis marsupialis DM43 and DM40, which confer natural resistance to snake venoms in this related marsupial (Neves-Ferreira et al 2000), could be found in Monodelphis. However, despite exhaustive searches of the current genome assembly, no substantially similar sequences to DM43 and DM40 were identified, perhaps indicating that these genes have evolved particularly rapidly.…”

Section: Dietary Adaptationmentioning

confidence: 99%

An analysis of the gene complement of a marsupial,Monodelphis domestica: Evolution of lineage-specific genes and giant chromosomes

Goodstadt¹,

Heger²,

Webber³

et al. 2007

Genome Res.

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The newly sequenced genome of Monodelphis domestica not only provides the out-group necessary to better understand our own eutherian lineage, but it enables insights into the innovative biology of metatherians. Here, we compare Monodelphis with Homo sequences from alignments of single nucleotides, genes, and whole chromosomes. Using PhyOP, we have established orthologs in Homo for 82% (15,250) of Monodelphis gene predictions. Those with single orthologs in each species exhibited a high median synonymous substitution rate (d S = 1.02), thereby explaining the relative paucity of aligned regions outside of coding sequences. Orthology assignments were used to construct a synteny map that illustrates the considerable fragmentation of Monodelphis and Homo karyotypes since their therian last common ancestor. Fifteen percent of Monodelphis genes are predicted, from their low divergence at synonymous sites, to have been duplicated in the metatherian lineage. The majority of Monodelphis-specific genes possess predicted roles in chemosensation, reproduction, adaptation to specific diets, and immunity. Using alignments of Monodelphis genes to sequences from either Homo or Trichosurus vulpecula (an Australian marsupial), we show that metatherian X chromosomes have elevated silent substitution rates and high G+C contents in comparison with both metatherian autosomes and eutherian chromosomes. Each of these elevations is also a feature of subtelomeric chromosomal regions. We attribute these observations to high rates of female-specific recombination near the chromosomal ends and within the X chromosome, which act to sustain or increase G+C levels by biased gene conversion. In particular, we propose that the higher G+C content of the Monodelphis X chromosome is a direct consequence of its small size relative to the giant autosomes.

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“…DM43, Venoms, and Snake Venom Metalloproteinases-DM43 was isolated from D. marsupialis serum as previously described (32). Lyophilized B. jararaca venom was from the Army Biology Institute (Rio de Janeiro, Brazil).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, two antihemorrhagic proteins, DM40 and DM43, were isolated from the antibothropic factor and characterized as SVMP inhibitors from the immunoglobulin supergene family. It was shown that these acid glycoproteins form noncovalent complexes with jararhagin, the main hemorrhagic metalloproteinase from B. jararaca venom (32).…”

Section: Dm43mentioning

confidence: 99%

Structural and Functional Analyses of DM43, a Snake Venom Metalloproteinase Inhibitor from Didelphis marsupialisSerum

Neves-Ferreira

Perales

Fox

et al. 2002

Journal of Biological Chemistry

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DM43, an opossum serum protein inhibitor of snake venom metalloproteinases, has been completely sequenced, and its disulfide bond pattern has been experimentally determined. It shows homology to human ␣ 1 Bglycoprotein, a plasma protein of unknown function and a member of the immunoglobulin supergene family. Size exclusion and dynamic laser light scattering data indicated that two monomers of DM43, each composed of three immunoglobulin-like domains, associated to form a homodimer in solution. Analysis of its glycan moiety showed the presence of N-acetylglucosamine, mannose, galactose, and sialic acid, most probably forming four biantennary N-linked chains. DM43 inhibited the fibrinogenolytic activities of bothrolysin and jararhagin and formed 1:1 stoichiometric stable complexes with both metalloproteinases. DM43 was ineffective against atrolysin C or A. No complex formation was detected between DM43 and jararhagin C, indicating the essential role of the metalloproteinase domain for interaction. Homology modeling based on the crystal structure of a killer cell inhibitory receptor suggested the existence of an I-type Ig fold, a hydrophobic dimerization surface and six surface loops potentially forming the metalloproteinase-binding surface on DM43.The natural resistance to envenomation by snakes observed in a few warm-blooded animals as well as in several snakes can be explained, in most cases, by the presence of soluble proteins in the resistant animals' sera, which can be grouped as inhibitors of either phospholipase A 2 (antimyotoxic and antineurotoxic factors) or snake venom metalloproteinases (SVMPs 1 ;antihemorrhagic factors) (for reviews, see Refs. 1-4). SVMPs are typically found in venom of Viperidae snakes (5). They are classified as members of the reprolysin subfamily of metalloproteinases (6), which also includes ADAMs, proteins composed of a disintegrin and metalloproteinase domain, which function in various physiological processes such as fertilization, cytokine shedding, and neurogenesis (7). SVMPs and ADAMs present many similar structural features as evidenced by their sequence and domain homologies (8). The reprolysins share with matrix metalloproteinases a conserved overall topology, a zinc-binding consensus motif, and a strictly conserved methionine near their active sites. For these reasons, SVMPs, ADAMs, and matrix metalloproteinases have been classified together as the metzincins (6, 9).Some SVMPs induce local hemorrhage apparently as a primary consequence of the degradation of extracellular matrix proteins, although their exact mechanism of action is still unclear (10 -12). Several SVMPs have been sequenced and/or cloned, and five crystal structures are available (13-17). SVMPs are organized into four classes (P-I to P-IV) according to their domain structure. The P-I class presents only the metalloproteinase domain. The P-II members have a disintegrin domain carboxyl-terminal to the proteinase domain. The P-III class has a disintegrin-like domain and a cysteine-rich domain following the protei...

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Isolation and characterization of DM40 and DM43, two snake venom metalloproteinase inhibitors from Didelphis marsupialis serum

Cited by 57 publications

References 45 publications

Snake antivenoms: adverse reactions and production technology

Snake antivenoms: adverse reactions and production technology

An analysis of the gene complement of a marsupial,Monodelphis domestica: Evolution of lineage-specific genes and giant chromosomes

Structural and Functional Analyses of DM43, a Snake Venom Metalloproteinase Inhibitor from Didelphis marsupialisSerum

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