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CatroxMP-II: a heme-modulated fibrinogenolytic metalloproteinase isolated from Crotalus atrox venom

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Abstract

It has been recently demonstrated that the hemotoxic venom activity of several species of snakes can be inhibited by carbon monoxide (CO) or a metheme forming agent. These and other data suggest that the biometal, heme, may be attached to venom enzymes and may be modulated by CO. A novel fibrinogenolytic metalloproteinase, named CatroxMP-II, was isolated and purified from the venom of a Crotalus atrox viper, and subjected to proteolysis and mass spectroscopy. An ion similar to the predicted singly charged m/z of heme at 617.18 was identified. Lastly, CORM-2 (tricarbonyldichlororuthenium (II) dimer, a CO releasing molecule) inhibited the fibrinogenolytic effects of CatroxMP-II on coagulation kinetics in human plasma. In conclusion, we present the first example of a snake venom metalloproteinase that is heme-bound and CO-inhibited.

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Funding

Funding for this project was provided by the NIH/ORIP, Viper Resource Grant 5P40OD010960-14 (NNTRC, Texas A&M University-Kingsville, Dr. E.E. Sánchez) and NIH/NHLBI Grant# 1R15HL137134-01 (Dr. M. Suntravat). Additional support was provided by the Robert A. Welch Foundation Department Grant, Grant number AC-0006 (TAMUK-Department of Chemistry). We would also like to thank, Nora Diaz DeLeon and Mark Hockmüller (NNTRC Serpentarium curator) and all the NNTRC personnel. This investigation was also supported by the Departments of Medicine and Anesthesiology.

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Authors and Affiliations

  1. Department of Chemistry, National Natural Toxins Research Center, Texas A&M University-Kingsville, Kingsville, TX, USA

    Montamas Suntravat & Elda E. Sánchez

  2. The Department of Medicine, Division of Endocrinology, University of Arizona College of Medicine, Tucson, AZ, USA

    Paul R. Langlais

  3. The Department of Anesthesiology, University of Arizona College of Medicine, P.O. Box 245114, 1501 North Campbell Avenue, Tucson, AZ, 85724-5114, USA

    Vance G. Nielsen

Authors
  1. Montamas Suntravat
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  2. Paul R. Langlais
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  3. Elda E. Sánchez
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  4. Vance G. Nielsen
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Corresponding author

Correspondence to Vance G. Nielsen.

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The authors have no conflicts of interest.

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Suntravat, M., Langlais, P.R., Sánchez, E.E. et al. CatroxMP-II: a heme-modulated fibrinogenolytic metalloproteinase isolated from Crotalus atrox venom. Biometals 31, 585–593 (2018). https://doi.org/10.1007/s10534-018-0107-5

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  • DOI: https://doi.org/10.1007/s10534-018-0107-5

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