Molecular cloning and functional characterization of two isoforms of dermonecrotic toxin from Loxosceles intermedia (Brown spider) venom gland

Silveira, Rafael Bertoni da; Pigozzo, Romine Bachmann; Chaim, Olga Meiri; Appel, Márcia Helena; Dreyfuss, Juliana Luporini; Toma, Leny; Mangili, Oldemir C.; Gremski, Waldemiro; Dietrich, Carl P.; Nader, Helena B.; Veiga, Sílvio Sanches

doi:10.1016/j.biochi.2006.02.008

Cited by 86 publications

(89 citation statements)

References 42 publications

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“…The interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by Mg 2+ ions, which are coordinated by the side chains of Glu 32 , Asp 34 , Asp 91 and solvent molecules [52]. Taking into account the knowledge of the 3-D structure of sphingomyelinases, the correlation between the occurrence of dermonecrosis with these toxins and the copresentation (or not) of phospholipase D activity by these proteins, the classification of dermonecrotic toxins into two different classes was proposed: class I -corresponding to the dermonecrotic toxins presenting one intra-chain disulfide bond and one extended hydrophobic loop; and class II -corresponding to the molecules containing an additional disulfide bond linking the catalytic loop to a second flexible loop.…”

Section: Several Toxins Have Been Previously Isolated Frommentioning

confidence: 99%

Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action

Santos¹,

Dias²,

Roberto³

et al. 2009

PPL

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Section: Several Toxins Have Been Previously Isolated Frommentioning

confidence: 99%

Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action

Santos¹,

Dias²,

Roberto³

et al. 2009

PPL

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“…In the case of ␤1A1 (SMase II) from L. laeta, SMase D activity has been observed but with a 3-fold higher K m value and a reported 2-fold lower reaction rate at saturating substrate concentrations compared with ␣III1 (SMase I) from the same species (26). References for structure and activity data are as follows: IsSMase (74); LiRecDT6 (11); LiRecDT7 (14); SMase I (8,18,27,35,59,64,75); Ll2 (8); LiRecDT4 (9); LgRec1 (76); Lr1/Lb1/Lb2 (8,25); L. arizonica ␣IB2bi (15,30); Lr2 (19,25); P1/P2 (77-79); LiRecDT1 (6,7,12,13,20,60); 3RLG (61); 3RLH (28); LiRecDT2 (7); LiRecDT5 (9); Lb3 (8,25); LiRecDT3 (7,10); and SMase II (26).…”

Section: Methodsmentioning

confidence: 99%

Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders

Lajoie

Roberts

Zobel-Thropp

et al. 2015

Journal of Biological Chemistry

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Background: Phospholipase D toxins from brown spider venoms can cause disease in humans. Results: Different toxin family members show specificity for lipid substrates with choline or ethanolamine headgroups or can be ambiguous. Conclusion: Spider phospholipase D toxins have evolved diverse substrate preferences. Significance: The diverse substrate preference may be significant for predation and the mammalian toxicity of venom.

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“…However, when the Hag-protease treated with PMSF, its aggregation property, including collagen induced aggregation was abolished suggesting the role of enzyme activity. So far only the sphingomyelinase-D and phospholipase-D enzymes, respectively, from L. intermedia and L. laeta spider venoms have been found to inhibit the aggregation of human platelets [2,3].…”

Section: Resultsmentioning

confidence: 99%

“…The whole venom of Loxosceles intermedia spider was shown to degrade Aa-and Bbchains but not the c-chain of fibrinogen. Sphingomyelinase-D and phospholipase-D, respectively from L. intermedia and Loxosceles laeta spiders were found to inhibit the aggregation of human platelets [3][4][5]. Although several enzymatic and non-enzymatic factors interfere in platelet function, the degradation of fibrinogen is due to the proteolytic activity of the venom.…”

Section: Introductionmentioning

confidence: 97%

Factor Xa-like and fibrin(ogen)olytic activities of a serine protease from Hippasa agelenoides spider venom gland extract

Sannaningaiah

Girish

Devaraj

et al. 2009

J Thromb Thrombolysis

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In the recent past, a low molecular mass serine protease, the Hag-protease that caused pro-coagulant activity and as well as local toxicity was isolated and characterized from the Hippasa agelenoides spider venom gland extract (Devaraja et al., Toxicon 52:130-138, 2008). In the current study, the pro-coagulant property has been investigated further and the results are presented. The Hag-protease reduced the re-calcification time of citrated human plasma. It reduced the activated partial thromboplastin time (APTT), and prothrombin time (PT) suggesting its participation in common pathway of blood coagulation. Interestingly, it coagulated the citrated human plasma in the absence of CaCl(2) but, it was lacking thrombin-like activity as it did not clot the purified fibrinogen. Strikingly, the enzyme coagulated the factor X deficient congenital human plasma, suggesting the factor Xa-like activity. However, the cumulative augmented activity was observed in presence of CaCl(2) and phospholipids. Further, the Hag-protease preferentially hydrolyzed the Aalpha chain and then the Bbeta-chain, but not the gamma-chain. As a result, truncated fibrinogen generated was lacking in the polymerization property. It hydrolyzed all the subunits of partially cross-liked fibrin clot (alpha-polymer, alpha-chain, beta-chain, and gamma-gamma dimers). Further, at low concentrations, the Hag-protease stimulated the aggregation of human platelets in platelet rich plasma, but at high concentrations caused spontaneous clumping. In contrast, it inhibited the collagen induced aggregation of washed human platelets. In summary, the present study for the first time reporting the factor Xa-like activity of a serine protease especially from the spider venom that exhibited opposing effects on hemostasis, the pro-coagulant activity and the anti-coagulant activity including fibrin(ogen)olytic and platelet aggregation inhibition activities.

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Molecular cloning and functional characterization of two isoforms of dermonecrotic toxin from Loxosceles intermedia (Brown spider) venom gland

Cited by 86 publications

References 42 publications

Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action

Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action

Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders

Factor Xa-like and fibrin(ogen)olytic activities of a serine protease from Hippasa agelenoides spider venom gland extract

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