tailieunhanh - Báo cáo Y học: Cloning and characterization of novel snake venom proteins that block smooth muscle contraction

In this study, we isolated a 25-kDa novel snake venom protein, designated ablomin, from the venom of the Japanese Mamushi snake (Agkistrodon blomhoffi). The amino-acid sequence of this protein was determined by peptide sequencing and cDNA cloning. The deduced sequence showed high similarity to helothermine from the Mexican beaded lizard (Heloderma horridum horridum), which blocks voltage-gated calcium and potassium channels, and ryanodine receptors. Ablomin blocked contraction of rat tail arterial smooth muscle elicited by high K+-induced depolarization in the –1 lM range, but did not block caffeine-stimulated contraction | Eur. J. Biochem. 269 2708-2715 2002 FEBS 2002 doi Cloning and characterization of novel snake venom proteins that block smooth muscle contraction Yasuo Yamazaki1. Hisashi Koike1. Yusuke Sugivama1. Kazuko Motovoshi1. Taeko Wada1 Shigeru Hishinuma2 Mitsuo Mita2 and Takashi Morita1 Departments of1 Biochemistry and 2Pharmacodynamics Meiji Pharmaceutical University Tokyo Japan In this study we isolated a 25-kDa novel snake venom protein designated ablomin from the venom of the Japanese Mamushi snake Agkistrodon blomhoffi . The amino-acid sequence of this protein was determined by peptide sequencing and cDNA cloning. The deduced sequence showed high similarity to helothermine from the Mexican beaded lizard Heloderma horridum horridum which blocks voltage-gated calcium and potassium channels and ryanodine receptors. Ablomin blocked contraction of rat tail arterial smooth muscle elicited by high K -induced depolarization in the M range but did not block caffeine-stimulated contraction. Furthermore we isolated three other proteins from snake venoms that are homologous to ablomin and cloned the corresponding cDNAs. Two of these homologous proteins triflin and latisemin also inhibited high K -induced contraction of the artery. These results indicate that several snake venoms contain novel proteins with neurotoxin-like activity. Keywords snake venom neurotoxin helothermine cysteine-rich secretory proteins ablomin. Over the past 30 years a plethora of toxins have been isolated from poisonous organisms such as snakes scorpions spiders and micro-organisms. These natural toxins use a variety of approaches to arrest the homeostatic mechanisms of other living organisms including disruption of intracellular signal transduction and cytoskeleton organization 1-4 and activation or inhibition of blood coagulation factors 5-10 . Toxins that block synaptic transmission called neurotoxins are widely distributed in venoms. These toxins include the .

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