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Open AccessReview

Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges

1
Laboratory of Toxinology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil
2
National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasilia 71605-001, Brazil
*
Author to whom correspondence should be addressed.
Academic Editors: José María Gutiérrez and Jay Fox
Toxins 2016, 8(9), 250; https://doi.org/10.3390/toxins8090250
Received: 18 June 2016 / Revised: 11 August 2016 / Accepted: 15 August 2016 / Published: 26 August 2016
(This article belongs to the Special Issue Snake Venom Metalloproteinases)
The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using “gold-standard” methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted. View Full-Text
Keywords: cross-linking; hydrogen/deuterium exchange; mass spectrometry; metalloendopeptidase inhibitor; modeling; natural immunity; natural resistance; snake venom; structure; therapeutic application cross-linking; hydrogen/deuterium exchange; mass spectrometry; metalloendopeptidase inhibitor; modeling; natural immunity; natural resistance; snake venom; structure; therapeutic application
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MDPI and ACS Style

Bastos, V.A.; Gomes-Neto, F.; Perales, J.; Neves-Ferreira, A.G.C.; Valente, R.H. Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges. Toxins 2016, 8, 250.

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