Abstract
The present study describes the purification and characterization of a hyaluronidase (DRHyal-II) from Daboia/Vipera russelli venom and its inhibition by β-3-(3-hydroxy-4-oxopyridyl) α-amino-propionic acid, the mimosine. Gel permeation and ion exchange chromatography were employed to isolate DRHyal-II. The molecular mass by MALDITOF mass spectrometry was found to be 28.3 kDa. Single band in reduced SDS-PAGE suggested the monomeric nature. It was optimally active at pH 5.5 and at 37°C and require 150 mM NaCl in the reaction mixture. It was specific to hyaluronan substrate and belongs to class-I or the neutral active enzymes. DRHyal-II was non-toxic by itself but, it potentiated the myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of hemorrhagic complex (HC). In in vitro experiments, mimosine inhibited the activity of DRHyal-II and the hyaluronidase activity of whole venom dose dependently. In in vivo experiments, mimosine inhibited the DRHyal-II potentiated myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of HC. The inhibition was due to the formation of DRHyal-II-mimosine inhibitory complex that resulted in significant structural changes at secondary and tertiary levels as evidenced by fluorescence emission and CD spectral studies. Hence, in this study an attempt was made to establish the possible role of hyaluronidase activity in the pathology of Daboia/Vipera russelli venom and the beneficial effects of its inhibition with special emphasis on the management of local toxicity.
Keywords: Hyaluronidase, spreading factor, extracellular matrix, hyaluronan, mimosine, local toxicity, snakebite, Daboia/Vipera russelli venom, MALDITOFmass spectrometry, hemorrhagic complex (HC), hemorrhagic activity
Current Topics in Medicinal Chemistry
Title: Daboia russelli Venom Hyaluronidase: Purification, Characterization and Inhibition by β-3-(3-Hydroxy-4-Oxopyridyl) α-Amino-Propionic Acid
Volume: 11 Issue: 20
Author(s): Y. H. Mahadeswaraswamy, B. Manjula, S. Devaraja, K. S. Girish and K. Kemparaju
Affiliation:
Keywords: Hyaluronidase, spreading factor, extracellular matrix, hyaluronan, mimosine, local toxicity, snakebite, Daboia/Vipera russelli venom, MALDITOFmass spectrometry, hemorrhagic complex (HC), hemorrhagic activity
Abstract: The present study describes the purification and characterization of a hyaluronidase (DRHyal-II) from Daboia/Vipera russelli venom and its inhibition by β-3-(3-hydroxy-4-oxopyridyl) α-amino-propionic acid, the mimosine. Gel permeation and ion exchange chromatography were employed to isolate DRHyal-II. The molecular mass by MALDITOF mass spectrometry was found to be 28.3 kDa. Single band in reduced SDS-PAGE suggested the monomeric nature. It was optimally active at pH 5.5 and at 37°C and require 150 mM NaCl in the reaction mixture. It was specific to hyaluronan substrate and belongs to class-I or the neutral active enzymes. DRHyal-II was non-toxic by itself but, it potentiated the myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of hemorrhagic complex (HC). In in vitro experiments, mimosine inhibited the activity of DRHyal-II and the hyaluronidase activity of whole venom dose dependently. In in vivo experiments, mimosine inhibited the DRHyal-II potentiated myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of HC. The inhibition was due to the formation of DRHyal-II-mimosine inhibitory complex that resulted in significant structural changes at secondary and tertiary levels as evidenced by fluorescence emission and CD spectral studies. Hence, in this study an attempt was made to establish the possible role of hyaluronidase activity in the pathology of Daboia/Vipera russelli venom and the beneficial effects of its inhibition with special emphasis on the management of local toxicity.
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Cite this article as:
H. Mahadeswaraswamy Y., Manjula B., Devaraja S., S. Girish K. and Kemparaju K., Daboia russelli Venom Hyaluronidase: Purification, Characterization and Inhibition by β-3-(3-Hydroxy-4-Oxopyridyl) α-Amino-Propionic Acid, Current Topics in Medicinal Chemistry 2011; 11 (20) . https://dx.doi.org/10.2174/156802611797633410
DOI https://dx.doi.org/10.2174/156802611797633410 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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