The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets

Eladio F. Sanchez; Francisco S. Schneider; Armando Yarleque; Marcia H. Borges; Michael Richardson; Suely G. Figueiredo; Karla S. Evangelista; Johannes A. Eble

doi:10.1016/j.abb.2010.01.010

The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets

Eladio F. Sanchez, Francisco S. Schneider, Armando Yarleque, Marcia H. Borges, Michael Richardson, Suely G. Figueiredo, Karla S. Evangelista, Johannes A. Eble

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

We report the isolation and structure-function relationship of a 23kDa metalloproteinase named atroxlysin-I from the venom of the Peruvian Bothrops atrox (Jergón). Atroxlysin is a P-I metalloproteinase and contains 204 residues. Its proteolytic activity towards dimethylcasein is enhanced by Ca⁺² but inhibited by EDTA, dithiothreitol, excessive Zn⁺² and α2-macroglobulin. Unlike other structurally homologous P-I metalloproteinases, atroxlysin-I causes hemorrhages. To examine its hemorrhagic activity mechanistically, we studied its function in vitro and in vivo. It cleaved the Ala₁₄-Leu₁₅ and Tyr₁₆-Leu₁₇ bonds in oxidized insulin B-chain and specifically hydrolyzed the α-chains of fibrin(ogen) in a dose- and time-dependent manner. Atroxlysin-I cleaved plasma fibronectin and other extracellular matrix proteins (collagens I and IV) and the triple-helical fragment CB3 of collagen IV, but did not degrade laminin-111. Complementarily, the laminin and collagen binding integrins α₇β₁ and α₁β₁ were cleaved by atroxlysin. Even without catalytic activity atroxlysin-I inhibited collagen- and ADP-triggered platelet aggregation.

Original language	English
Pages (from-to)	9-20
Number of pages	12
Journal	Archives of Biochemistry and Biophysics
Volume	496
Issue number	1
DOIs	https://doi.org/10.1016/j.abb.2010.01.010
State	Published - Apr 2010

Bibliographical note

Funding Information:
The authors thank to Drs. M.R. Fontes and A.A. Takeda (Dept. of Physics and Biophysics, UNESP, Saõ Paulo, Brazil) for the determination of CD spectra. We also thank Mr. G. Naumann for his technical assistance with zinc analysis. This work was supported by FAPEMIG Grants No: CBB 359/06 and APQ-2673-40.1/07 to E.F.S., J.A.E. receives financial support of the DFG (Grants: SFB 815 project A6, SFB/TR23 project A8 and the Excellence Cluster Cardio-Pulmonary System).

Keywords

Atroxlysin
Hemostasis
Metalloproteinase
Platelets
Snake venom

Access to Document

10.1016/j.abb.2010.01.010

Cite this

Sanchez, E. F., Schneider, F. S., Yarleque, A., Borges, M. H., Richardson, M., Figueiredo, S. G., Evangelista, K. S., & Eble, J. A. (2010). The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets. Archives of Biochemistry and Biophysics, 496(1), 9-20. https://doi.org/10.1016/j.abb.2010.01.010

@article{bfca72448bab41efbf6f552a5a856954,

title = "The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jerg{\'o}n) snake venom acts both on blood vessel ECM and platelets",

abstract = "We report the isolation and structure-function relationship of a 23kDa metalloproteinase named atroxlysin-I from the venom of the Peruvian Bothrops atrox (Jerg{\'o}n). Atroxlysin is a P-I metalloproteinase and contains 204 residues. Its proteolytic activity towards dimethylcasein is enhanced by Ca+2 but inhibited by EDTA, dithiothreitol, excessive Zn+2 and α2-macroglobulin. Unlike other structurally homologous P-I metalloproteinases, atroxlysin-I causes hemorrhages. To examine its hemorrhagic activity mechanistically, we studied its function in vitro and in vivo. It cleaved the Ala14-Leu15 and Tyr16-Leu17 bonds in oxidized insulin B-chain and specifically hydrolyzed the α-chains of fibrin(ogen) in a dose- and time-dependent manner. Atroxlysin-I cleaved plasma fibronectin and other extracellular matrix proteins (collagens I and IV) and the triple-helical fragment CB3 of collagen IV, but did not degrade laminin-111. Complementarily, the laminin and collagen binding integrins α7β1 and α1β1 were cleaved by atroxlysin. Even without catalytic activity atroxlysin-I inhibited collagen- and ADP-triggered platelet aggregation.",

keywords = "Atroxlysin, Hemostasis, Metalloproteinase, Platelets, Snake venom",

author = "Sanchez, {Eladio F.} and Schneider, {Francisco S.} and Armando Yarleque and Borges, {Marcia H.} and Michael Richardson and Figueiredo, {Suely G.} and Evangelista, {Karla S.} and Eble, {Johannes A.}",

note = "Funding Information: The authors thank to Drs. M.R. Fontes and A.A. Takeda (Dept. of Physics and Biophysics, UNESP, Sa{\~o} Paulo, Brazil) for the determination of CD spectra. We also thank Mr. G. Naumann for his technical assistance with zinc analysis. This work was supported by FAPEMIG Grants No: CBB 359/06 and APQ-2673-40.1/07 to E.F.S., J.A.E. receives financial support of the DFG (Grants: SFB 815 project A6, SFB/TR23 project A8 and the Excellence Cluster Cardio-Pulmonary System).",

year = "2010",

month = apr,

doi = "10.1016/j.abb.2010.01.010",

language = "Ingl{\'e}s",

volume = "496",

pages = "9--20",

journal = "Archives of Biochemistry and Biophysics",

issn = "0003-9861",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets

AU - Sanchez, Eladio F.

AU - Schneider, Francisco S.

AU - Yarleque, Armando

AU - Borges, Marcia H.

AU - Richardson, Michael

AU - Figueiredo, Suely G.

AU - Evangelista, Karla S.

AU - Eble, Johannes A.

N1 - Funding Information: The authors thank to Drs. M.R. Fontes and A.A. Takeda (Dept. of Physics and Biophysics, UNESP, Saõ Paulo, Brazil) for the determination of CD spectra. We also thank Mr. G. Naumann for his technical assistance with zinc analysis. This work was supported by FAPEMIG Grants No: CBB 359/06 and APQ-2673-40.1/07 to E.F.S., J.A.E. receives financial support of the DFG (Grants: SFB 815 project A6, SFB/TR23 project A8 and the Excellence Cluster Cardio-Pulmonary System).

PY - 2010/4

Y1 - 2010/4

N2 - We report the isolation and structure-function relationship of a 23kDa metalloproteinase named atroxlysin-I from the venom of the Peruvian Bothrops atrox (Jergón). Atroxlysin is a P-I metalloproteinase and contains 204 residues. Its proteolytic activity towards dimethylcasein is enhanced by Ca+2 but inhibited by EDTA, dithiothreitol, excessive Zn+2 and α2-macroglobulin. Unlike other structurally homologous P-I metalloproteinases, atroxlysin-I causes hemorrhages. To examine its hemorrhagic activity mechanistically, we studied its function in vitro and in vivo. It cleaved the Ala14-Leu15 and Tyr16-Leu17 bonds in oxidized insulin B-chain and specifically hydrolyzed the α-chains of fibrin(ogen) in a dose- and time-dependent manner. Atroxlysin-I cleaved plasma fibronectin and other extracellular matrix proteins (collagens I and IV) and the triple-helical fragment CB3 of collagen IV, but did not degrade laminin-111. Complementarily, the laminin and collagen binding integrins α7β1 and α1β1 were cleaved by atroxlysin. Even without catalytic activity atroxlysin-I inhibited collagen- and ADP-triggered platelet aggregation.

AB - We report the isolation and structure-function relationship of a 23kDa metalloproteinase named atroxlysin-I from the venom of the Peruvian Bothrops atrox (Jergón). Atroxlysin is a P-I metalloproteinase and contains 204 residues. Its proteolytic activity towards dimethylcasein is enhanced by Ca+2 but inhibited by EDTA, dithiothreitol, excessive Zn+2 and α2-macroglobulin. Unlike other structurally homologous P-I metalloproteinases, atroxlysin-I causes hemorrhages. To examine its hemorrhagic activity mechanistically, we studied its function in vitro and in vivo. It cleaved the Ala14-Leu15 and Tyr16-Leu17 bonds in oxidized insulin B-chain and specifically hydrolyzed the α-chains of fibrin(ogen) in a dose- and time-dependent manner. Atroxlysin-I cleaved plasma fibronectin and other extracellular matrix proteins (collagens I and IV) and the triple-helical fragment CB3 of collagen IV, but did not degrade laminin-111. Complementarily, the laminin and collagen binding integrins α7β1 and α1β1 were cleaved by atroxlysin. Even without catalytic activity atroxlysin-I inhibited collagen- and ADP-triggered platelet aggregation.

KW - Atroxlysin

KW - Hemostasis

KW - Metalloproteinase

KW - Platelets

KW - Snake venom

UR - http://www.scopus.com/inward/record.url?scp=77950460487&partnerID=8YFLogxK

U2 - 10.1016/j.abb.2010.01.010

DO - 10.1016/j.abb.2010.01.010

M3 - Artículo

C2 - 20102699

AN - SCOPUS:77950460487

SN - 0003-9861

VL - 496

SP - 9

EP - 20

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

IS - 1

ER -

The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this