Tryptophan and aspartic acid residues present in the glycerophosphoryl diester phosphodiesterase (GDPD) domain of the Loxosceles laeta phospholipase D are essential for substrate recognition

Catalán, Alejandro; Cortés, William; Muñoz, Christian; Araya, Jorge E.

doi:10.1016/j.toxicon.2014.01.011

Cited by 13 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these species, only L. laeta presented Class I and Class II isoforms. The other sequences were obtained by sequencing cloned PCR products with heterologous primers ([ 10 , 33 ] and Genbank). Except for L. laeta , L. gaucho and an unidentified species ( L. sp .…”

Section: Discussionmentioning

confidence: 99%

Adaptive evolution in the toxicity of a spider’s venom enzymes

et al. 2015

View full text Add to dashboard Cite

BackgroundSphingomyelinase D is the main toxin present in the venom of Loxosceles spiders. Several isoforms present in these venoms can be structurally classified in two groups. Class I Sphingomyelinase D contains a single disulphide bridge and variable loop. Class II Sphingomyelinase D presents an additional intrachain disulphide bridge that links a flexible loop with a catalytic loop. These classes exhibit differences in their toxic potential. In this paper we address the distribution of the structural classes of SMase D within and among species of spiders and also their evolutionary origin by means of phylogenetic analyses. We also conducted tests to assess the action of natural selection in their evolution combined to structural modelling of the affected sites.ResultsThe majority of the Class I enzymes belong to the same clade, which indicates a recent evolution from a single common ancestor. Positively selected sites are located on the catalytic interface, which contributes to a distinct surface charge distribution between the classes. Sites that may prevent the formation of an additional bridge were found in Class I enzymes.ConclusionsThe evolution of Sphingomyelinase D has been driven by natural selection toward an increase in noxiousness, and this might help explain the toxic variation between classes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0561-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Adaptive evolution in the toxicity of a spider’s venom enzymes

et al. 2015

View full text Add to dashboard Cite

show abstract

“…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%

“…8, below). GDPDs are distantly related to the SicTox proteins (27,64,65), and their mechanism has been proposed to proceed through a five-membered cyclic phosphate intermediate (45) analogous to the product of the toxin action on lysophospholipids (15). We felt that the conformation of the glycerol phosphate in the GDPD active site was a reasonable model for the phosphoglycerol portion of LPC or LPE bound to the toxin in a catalytically competent mode.…”

Section: Structural Comparison Of St_␤ib1i With Other Sictox Proteinsmentioning

confidence: 99%

“…One possibility is that the SicTox mechanism is homologous to the first step of the mechanism of GDPD enzymes, which are distantly related (27,64,65). GDPDs hydrolyze phosphoglycerol substrates and have been proposed to form a cyclic intermediate analogous to the lipid product of the action of SicTox enzymes on lysophospholipids (45).…”

Section: Structural Comparison Of St_␤ib1i With Other Sictox Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders

Lajoie

Roberts

Zobel-Thropp

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

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.

show abstract

“…These PLDs display only residual activities for dermonecrosis (L. intermedia isoforms) and catalysis (all isoforms). Another experimental data that strengthens the importance of the aromatic triple region (Y228-Y229-W230) in the Loxosceles venom PLDs was demonstrated by substitution of tryptophan (W230A), which resulted in an enzyme that neither degraded sphingomyelin nor possessed hemolytic activity [68]. This same study showed that the mutation D259G (corresponding to D233 when numbering excludes amino acids from the signal peptide) produced loss of activity upon sphingomyelin, and mutation S262A (corresponding to S236) caused a decrease in the enzymatic activity upon the same substrate.…”

Section: Structural Organization and The Catalytic Mechanisms Of Browmentioning

confidence: 94%

Forty Years of the Description of Brown Spider Venom Phospholipases-D

Gremski

Justa

Silva

et al. 2020

Toxins

View full text Add to dashboard Cite

Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and loxoscelism. Present and future aspects of loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field.

show abstract

Tryptophan and aspartic acid residues present in the glycerophosphoryl diester phosphodiesterase (GDPD) domain of the Loxosceles laeta phospholipase D are essential for substrate recognition

Cited by 13 publications

References 16 publications

Adaptive evolution in the toxicity of a spider’s venom enzymes

Adaptive evolution in the toxicity of a spider’s venom enzymes

Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders

Forty Years of the Description of Brown Spider Venom Phospholipases-D

Contact Info

Product

Resources

About