Characterization of major zinc containing myonecrotic and procoagulant metalloprotease 'malabarin' from non lethal Trimeresurus malabaricus snake venom with thrombin like activity: Its neutralization by chelating agents

C. D. Raghavendra Gowda, H. V. Shivaprasad, R. Venkatesh Kumar, R. Rajesh, Y. K. Saikumari, B. M. Frey, F. J. Frey, B. K. Sharath, B. S. Vishwanath

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

A major myonecrotic zinc containing metalloprotease 'malabarin' with thrombin like activity was purified bythe combination of gel permeation and anion exchange chromatography from T. malabaricus snake venom. MALDI-TOFanalysis of malabarin indicated a molecular mass of 45.76 kDa and its N-terminal sequence was found to be Ile-Ile-Leu-Pro(Leu)-Ile-Gly-Val-Ile-Leu(Glu)-Thr-Thr. Atomic absorption spectral analysis of malabarin raveled the association ofzinc metalion. Malabarin is not lethal when injected i.p. or i.m. but causes extensive hemorrhage and degradation of muscle tissue within 24 hours. Sections of muscle tissue under light microscope revealed hemorrhage and congestion of blood vessel during initial stage followed by extensive muscle fiber necrosis with elevated levels of serum creatine kinase and lactate dehydrogenase activity. Malabarin also exhibited strong procoagulant action and its procoagulant action is due to thrombin like activity; it hydrolyzes fibrinogen to form fibrin clot. The enzyme preferentially hydrolyzes Aα followed by Bβ subunits of fibrinogen from the N-terminal region and the released products were identified as fibrinopeptide A and fibrinopeptide B by MALDI. The myonecrotic, fibrinogenolytic and subsequent procoagulant activities of malabarin was neutralized by specific metalloprotease inhibitors such as EDTA, EGTA and 1, 10-phenanthroline but not by PMSF a specificserine protease inhibitor. Since there is no antivenom available to neutralize local toxicity caused by T. malabaricus snakebite, EDTA chelation therapy may have more clinical relevance over conventional treatment.

Original languageEnglish (US)
Pages (from-to)2578-2588
Number of pages11
JournalCurrent Topics in Medicinal Chemistry
Volume11
Issue number20
DOIs
StatePublished - Oct 2011

All Science Journal Classification (ASJC) codes

  • Drug Discovery

Fingerprint Dive into the research topics of 'Characterization of major zinc containing myonecrotic and procoagulant metalloprotease 'malabarin' from non lethal Trimeresurus malabaricus snake venom with thrombin like activity: Its neutralization by chelating agents'. Together they form a unique fingerprint.

  • Cite this