Comparison of venom composition and biological activities of the subspecies Crotalus lepidus lepidus, Crotalus lepidus klauberi and Crotalus lepidus morulus from Mexico

Martínez-Romero, Gerardo; Rucavado, Alexandra; Lazcano, David; Gutiérrez, José Marı́a; Borja, Miguel; Lomonte, Bruno; Garza-Garcı́a, Yolanda; Zugasti–Cruz, Alejandro

doi:10.1016/j.toxicon.2013.05.006

Cited by 15 publications

(11 citation statements)

References 32 publications

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“…Exceptions include species that represent the greatest risks to humans, such as C. simus [ 5 , 6 ] and C. scutulatus scutulatus [ 7 ]. Several recent studies have also examined the venom compositional patterns of the diminutive C. lepidus [ 8 , 9 , 10 ] and C. willardi [ 10 ] subspecies.…”

Section: Introductionmentioning

confidence: 99%

Venom Ontogeny in the Mexican Lance-Headed Rattlesnake (Crotalus polystictus)

Mackessy

Leroy

Mociño-Deloya

et al. 2018

Toxins

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As trophic adaptations, rattlesnake venoms can vary in composition depending on several intrinsic and extrinsic factors. Ontogenetic changes in venom composition have been documented for numerous species, but little is known of the potential age-related changes in many rattlesnake species found in México. In the current study, venom samples collected from adult and neonate Crotalus polystictus from Estado de México were subjected to enzymatic and electrophoretic analyses, toxicity assays (LD50), and MALDI-TOF mass spectrometry, and a pooled sample of adult venom was analyzed by shotgun proteomics. Electrophoretic profiles of adult males and females were quite similar, and only minor sex-based variation was noted. However, distinct differences were observed between venoms from adult females and their neonate offspring. Several prominent bands, including P-I and P-III snake venom metalloproteinases (SVMPs) and disintegrins (confirmed by MS/MS) were present in adult venoms and absent/greatly reduced in neonate venoms. Age-dependent differences in SVMP, kallikrein-like, phospholipase A2 (PLA2), and L-amino acid oxidase (LAAO) activity levels were confirmed by enzymatic activity assays, and like many other rattlesnake species, venoms from adult snakes have higher SVMP activity than neonate venoms. Conversely, PLA2 activity was approximately 2.5 × greater in venoms from neonates, likely contributing to the increased toxicity (neonate venom LD50 = 4.5 μg/g) towards non-Swiss albino mice when compared to adult venoms (LD50 = 5.5 μg/g). Thrombin-like (TLE) and phosphodiesterase activities did not vary significantly with age. A significant effect of sex (between adult male and adult female venoms) was also observed for SVMP, TLE, and LAAO activities. Analysis of pooled adult venom by LC-MS/MS identified 14 toxin protein families, dominated by bradykinin-inhibitory peptides, SVMPs (P-I, P-II and P-III), disintegrins, PLA2s, C-type-lectins, CRiSPs, serine proteinases, and LAAOs (96% of total venom proteins). Neonate and adult C. polystictus in this population consume almost exclusively mammals, suggesting that age-based differences in composition are related to physical differences in prey (e.g., surface-to-volume ratio differences) rather than taxonomic differences between prey. Venoms from adult C. polystictus fit a Type I pattern (high SVMP activity, lower toxicity), which is characteristic of many larger-bodied rattlesnakes of North America.

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Section: Introductionmentioning

confidence: 99%

Venom Ontogeny in the Mexican Lance-Headed Rattlesnake (Crotalus polystictus)

Mackessy

Leroy

Mociño-Deloya

et al. 2018

Toxins

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“…The S' 1 -pocket of GP1 was more structurally homologous to the S' 1 -pockets of the atrolysins than of the other three C. s. scutulatus metalloproteinases, suggesting that GP1 and the atrolysins recognize similar substrates to produce hemorrhage. The depth and accessibility of the alternate binding cavity conformed by the S' 1 -pocket is thought to determine the ability of hemorrhagic metalloproteinases for binding bulky amino acid side chains (i.e., tyrosine and tryptophan) as found in collagen type IV (Gly-X), a critical factor that determines hemorrhagic activity of metalloproteinases [28]. In the present study, an analysis of the depth or the distance between the S' 1 -pocket and the catalytic site cavity revealed no significant differences or correlation to hemorrhagic activities for the C. s. scutulatus metalloproteinase models.…”

Section: Discussionmentioning

confidence: 99%

“…Rattlesnake venom belonging to the Crotalus genus exhibits high variability in snake venom composition and shows complex pharmacological profiles and in biochemicalassociated activities [27][28][29][30]. Recently, a series of elegant transcriptome sequencing-based approaches have shown that rattlesnake venom glands from C. adamanteus are composed mainly of serine proteases, while a small fraction of venom consists of Zn +2 -dependent metalloproteinases [31].…”

Section: Introductionmentioning

confidence: 99%

Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities

Dagda

Gasanov²,

Zhang³

et al. 2014

J Biol Phys

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Rattlesnake venom can differ in composition and in metalloproteinase-associated activities. The molecular basis for this intra-species variation in Crotalus scutulatus scutulatus (Mojave rattlesnake) remains an enigma. To understand the molecular basis for intra-species variation of metalloproteinase-associated activities, we modeled the threedimensional structures of four metalloproteinases based on the amino acid sequence of four variations of the proteinase domain of the C. s. scutulatus metalloproteinase gene (GP1, GP2, GP3, and GP4). For comparative purposes, we modeled the atrolysin metalloproteinases of C. atrox as well. All molecular models shared the same topology. While the atrolysin metalloproteinase molecular models contained highly conserved substrate binding sites, the Mojave rattlesnake metalloproteinases showed higher structural divergence when superimposed onto each other. The highest structural divergence among the four C. s. scutulatus molecular models was located at the northern cleft wall and the S' 1 -pocket of the substrate binding site, molecular regions that modulate substrate selectivity. Molecular dynamics and field potential maps for each C. s. scutulatus metalloproteinase model demonstrated that the non-hemorrhagic metalloproteinases (GP2 and GP3) contain highly basic molecular and field potential surfaces while the hemorrhagic metalloproteinases GP1 and atrolysin C showed extensive acidic field potential maps and shallow but less dynamic active site pockets. Hence, differences in the spatial arrangement of the northern cleft wall, the S' 1 -pocket, and the physico-chemical environment surrounding the catalytic site contribute to differences in metalloproteinase activities in the Mojave rattlesnake. Our results provide a structural basis for variation of metalloproteinase-associated activities in the rattlesnake venom of the Mojave rattlesnake.

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“…41 studies reported the relative abundance of protein constituents. [40] C. cerastes 3FTx, 5 NT, BPP, CRiSP, CTL, Dis, ficolin, Hya, Kun, LAAO, MYO, NGF, PDE, PLA 2 , SVMP P-II/III, SVSP, VEGF, vespryn, WAP [98,[100][101][102] C. durissus 3FTx, achase, aminopeptidase, angiogenin, BPP, carboxypeptidase, CNP, CRiSP, CTL, CysProt inhibitor, CysProt, dipeptidyl peptidase, Dis, FGF, fraction 5, Hya, Kazal, Kun, LAAO, lipase, MYO, NGF, PDGF, PLA 2 (non-CRTX, CRTX), PLB, PLD, Serpin-like, SVMP inhibitor, SVMP P-III, SVSP, VEGF, vespryn, WAP [45,64,[103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] C. enyo SVSP, SVMP P-I/III, PLA 2 [40] C. horridus 5 -NT, BPP, CNP, CRiSP, Dis, EGF-like, GC, Hya, Kun, LAAO, MYO, neurotrophic factor, NGF, PDE, PLA 2 , SVMP P-I/III, SVSP, VEGF, vespryn [29,119,120] C. lepidus 5 NT, CRiSP, CTL, Dis, LAAO, PDE, PLA 2 , SVMP-P-I/III, SVSP (TLE, kallikrein) [49,[121][122][123] C. mitchelli LAAO, SVSP, PLA 2 (CRTX/MTX) [40,124,125] C. molossus Dis, LAAO, MYO, PLA 2 , SVMP P-I/III, SVSP (TLE) [58,98,[126][127][128][129][130]…”

Section: Venom Constituents In Crotalus Venommentioning

confidence: 99%

A Meta-Analysis of the Protein Components in Rattlesnake Venom

Deshwal

Phan

Datta

et al. 2021

Toxins

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The specificity and potency of venom components give them a unique advantage in developing various pharmaceutical drugs. Though venom is a cocktail of proteins, rarely are the synergy and association between various venom components studied. Understanding the relationship between various components of venom is critical in medical research. Using meta-analysis, we observed underlying patterns and associations in the appearance of the toxin families. For Crotalus, Dis has the most associations with the following toxins: PDE; BPP; CRL; CRiSP; LAAO; SVMP P-I and LAAO; SVMP P-III and LAAO. In Sistrurus venom, CTL and NGF have the most associations. These associations can predict the presence of proteins in novel venom and understand synergies between venom components for enhanced bioactivity. Using this approach, the need to revisit the classification of proteins as major components or minor components is highlighted. The revised classification of venom components is based on ubiquity, bioactivity, the number of associations, and synergies. The revised classification can be expected to trigger increased research on venom components, such as NGF, which have high biomedical significance. Using hierarchical clustering, we observed that the genera’s venom compositions were similar, based on functional characteristics rather than phylogenetic relationships.

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Comparison of venom composition and biological activities of the subspecies Crotalus lepidus lepidus, Crotalus lepidus klauberi and Crotalus lepidus morulus from Mexico

Cited by 15 publications

References 32 publications

Venom Ontogeny in the Mexican Lance-Headed Rattlesnake (Crotalus polystictus)

Venom Ontogeny in the Mexican Lance-Headed Rattlesnake (Crotalus polystictus)

Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities

A Meta-Analysis of the Protein Components in Rattlesnake Venom

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