Inhibition of Snake Venom Metalloproteinase by β-Lactoglobulin Peptide from Buffalo (Bubalus bubalis) Colostrum.
Bioactive peptide research has experienced considerable therapeutic interest owing to varied physiological functions, efficacy in excretion, and tolerability of peptides. Colostrum is a rich natural source of bioactive peptides with many properties elucidated such as anti-thrombotic, anti-hypertensive, opioid, immunomodulatory, etc. In this study, a variant peptide derived from β-lactoglobulin from buffalo colostrum was evaluated for the anti-ophidian property by targeting snake venom metalloproteinases. These are responsible for rapid local tissue damages that develop after snakebite such as edema, hemorrhage, myonecrosis, and extracellular matrix degradation. The peptide identified by LC-MS/MS effectively neutralized hemorrhagic activity of the Echis carinatus venom in a dose-dependent manner. Histological examinations revealed that the peptide mitigated basement membrane degradation and accumulation of inflammatory leucocytes at the venom-injected site. Inhibition of proteolytic activity was evidenced in both casein and gelatin zymograms. Also, inhibition of fibrinolytic and fibrinogenolytic activities was seen. The UV-visible spectral study implicated Zn2+chelation, which was further confirmed by molecular docking and dynamic studies by assessing molecular interactions, thus implicating the probable mechanism for inhibition of venom-induced proteolytic and hemorrhagic activities. The present investigation establishes newer vista for the BLG-col peptide with anti-ophidian efficacy as a promising candidate for therapeutic interventions.
DOS in Biotechnology, University of Mysore, Manasagangotri, Mysore, 570 006, India.
Ashok
A
Arpitha
Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-171 77, Stockholm, Sweden.
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Sebastin Santhosh
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
A C
AC
Rohit
DOSR in Biochemistry, Tumkur University, Tumkur, 572103, India.
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KS
Girish
Schrödinger, Bangalore, 560086, India.
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D
Vinod
DOS in Biotechnology, University of Mysore, Manasagangotri, Mysore, 570 006, India. hsa.uom@gmail.com.
H S
HS
Aparna
D000595:Amino Acid Sequence; D000818:Animals; D002020:Buffaloes; D002364:Caseins / Q000378:metabolism; D003126:Colostrum / Q000737:chemistry*; D003198:Computer Simulation; D004487:Edema / Q000188:drug therapy; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D006868:Hydrolysis; D007782:Lactoglobulins / Q000737:chemistry*; D045726:Metalloproteases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D059748:Proteolysis / Q000187:drug effects; D012867:Skin / Q000187:drug effects; D014757:Viper Venoms / Q000201:enzymology*; D017819:Viperidae
D002364:Caseins; D007782:Lactoglobulins; D009842:Oligopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D014757:Viper Venoms; D005337:Fibrin; D005340:Fibrinogen; D045726:Metalloproteases
Colostrum; Molecular dynamics; Peptide; Snake venom metalloproteinases; β-Lactoglobulin