MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism
| Autor: | Chitra Gupta, Dinakar M. Salunke, Deepak T. Nair, Ashish Kumar |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Proteases Molecular Sequence Data Immunology Snake Bites Venom Viper Venoms Crystallography X-Ray complex mixtures Biochemistry Neutralization Mice 03 medical and health sciences medicine Animals Humans Amino Acid Sequence Molecular Biology Plant Proteins Mice Inbred BALB C Plants Medicinal 030102 biochemistry & molecular biology biology Cell Biology biology.organism_classification medicine.disease Antibodies Neutralizing Mucuna Expressions of Concern Snake bites Protease inhibitor (biology) 030104 developmental biology Plant protein Snake venom Seeds Female Immunization Mucuna pruriens Snake Venoms medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 291:11373-11384 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|