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Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis
Authors:Kang Tse Siang  Georgieva Dessislava  Genov Nikolay  Murakami Mário T  Sinha Mau  Kumar Ramasamy P  Kaur Punit  Kumar Sanjit  Dey Sharmistha  Sharma Sujata  Vrielink Alice  Betzel Christian  Takeda Soichi  Arni Raghuvir K  Singh Tej P  Kini R Manjunatha
Institution:Department of Pharmacy, National University of Singapore, Singapore.
Abstract:Snake venoms are cocktails of enzymes and non-enzymatic proteins used for both the immobilization and digestion of prey. The most common snake venom enzymes include acetylcholinesterases, l-amino acid oxidases, serine proteinases, metalloproteinases and phospholipases A(2) . Higher catalytic efficiency, thermal stability and resistance to proteolysis make these enzymes attractive models for biochemists, enzymologists and structural biologists. Here, we review the structures of these enzymes and describe their structure-based mechanisms of catalysis and inhibition. Some of the enzymes exist as protein complexes in the venom. Thus we also discuss the functional role of non-enzymatic subunits and the pharmacological effects of such protein complexes. The structures of inhibitor-enzyme complexes provide ideal platforms for the design of potent inhibitors which are useful in the development of prototypes and lead compounds with potential therapeutic applications.
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