Protease activity profiling of snake venoms using high-throughput peptide screening

Konstantinos Kalogeropoulos, Andreas Frederik Treschow, Ulrich Auf Dem Keller, Teresa Escalante, Alexandra Rucavado, José María Gutiérrez, Andreas Hougaard Laustsen, Christopher T. Workman*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.

Original languageEnglish
Article number170
JournalToxins
Volume11
Issue number3
Number of pages23
ISSN2072-6651
DOIs
Publication statusPublished - 2019

Keywords

  • Enzymatic profile
  • High-throughput
  • Modeling
  • Peptide substrates
  • Proteinase activity
  • Screening
  • Snake venom proteinases

Cite this

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title = "Protease activity profiling of snake venoms using high-throughput peptide screening",
abstract = "Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.",
keywords = "Enzymatic profile, High-throughput, Modeling, Peptide substrates, Proteinase activity, Screening, Snake venom proteinases",
author = "Konstantinos Kalogeropoulos and Treschow, {Andreas Frederik} and {Auf Dem Keller}, Ulrich and Teresa Escalante and Alexandra Rucavado and Guti{\'e}rrez, {Jos{\'e} Mar{\'i}a} and Laustsen, {Andreas Hougaard} and Workman, {Christopher T.}",
year = "2019",
doi = "10.3390/toxins11030170",
language = "English",
volume = "11",
journal = "Toxins",
issn = "2072-6651",
publisher = "M D P I AG",
number = "3",

}

Protease activity profiling of snake venoms using high-throughput peptide screening. / Kalogeropoulos, Konstantinos; Treschow, Andreas Frederik; Auf Dem Keller, Ulrich; Escalante, Teresa; Rucavado, Alexandra; Gutiérrez, José María; Laustsen, Andreas Hougaard; Workman, Christopher T.

In: Toxins, Vol. 11, No. 3, 170, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Protease activity profiling of snake venoms using high-throughput peptide screening

AU - Kalogeropoulos, Konstantinos

AU - Treschow, Andreas Frederik

AU - Auf Dem Keller, Ulrich

AU - Escalante, Teresa

AU - Rucavado, Alexandra

AU - Gutiérrez, José María

AU - Laustsen, Andreas Hougaard

AU - Workman, Christopher T.

PY - 2019

Y1 - 2019

N2 - Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.

AB - Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.

KW - Enzymatic profile

KW - High-throughput

KW - Modeling

KW - Peptide substrates

KW - Proteinase activity

KW - Screening

KW - Snake venom proteinases

U2 - 10.3390/toxins11030170

DO - 10.3390/toxins11030170

M3 - Journal article

VL - 11

JO - Toxins

JF - Toxins

SN - 2072-6651

IS - 3

M1 - 170

ER -