MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism.

Abstract

Mortality due to snakebite is a serious public health problem, and available therapeutics are known to induce debilitating side effects. Traditional medicine suggests that seeds of Mucuna pruriens can provide protection against the effects of snakebite. Our aim is to identify the protein(s) that may be important for snake venom neutralization and elucidate its mechanism of action. To this end, we have identified and purified a protein from M. pruriens, which we have named MP-4. The full-length polypeptide sequence of MP-4 was obtained through N-terminal sequencing of peptide fragments. Sequence analysis suggested that the protein may belong to the Kunitz-type protease inhibitor family and therefore may potentially neutralize the proteases present in snake venom. Using various structural and biochemical tools coupled with in vivo assays, we are able to show that MP-4 does not afford direct protection against snake venom because it is actually a poor inhibitor of serine proteases. Further experiments showed that antibodies generated against MP-4 cross-react with the whole venom and provide protection to mice against Echis carinatus snake venom. This study shows that the MP-4 contributes significantly to the snake venom neutralization activity of M. pruriens seeds through an indirect antibody-mediated mechanism.

• Authors: Ashish Kumar, Chitra Gupta, Deepak T Nair, Dinakar M Salunke
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 291 Issue 21 Pg. 11373-84 (May 20 2016) ISSN: 1083-351X [Electronic] United States
• PMID: 26987900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Antibodies, Neutralizing
• Plant Proteins
• Snake Venoms
• Viper Venoms

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Neutralizing (biosynthesis)
• Crystallography, X-Ray
• Female
• Humans
• Immunization
• Mice
• Mice, Inbred BALB C
• Models, Molecular
• Molecular Sequence Data
• Mucuna (chemistry, genetics)
• Plant Proteins (genetics, immunology, pharmacology)
• Plants, Medicinal
• Seeds (chemistry, genetics)
• Snake Bites (immunology, therapy)
• Snake Venoms (antagonists & inhibitors, immunology)
• Viper Venoms (antagonists & inhibitors, immunology)