Oxiagin from the Naja oxiana cobra venom is the first reprolysin inhibiting the classical pathway of complement

Autor: Elena V. Kryukova, Yuri N. Utkin, Victor I. Tsetlin, Alexey V. Osipov, Alexey A. Zinchenko, Batozhab B. Shoibonov, Vladimir M. Lakhtin
Rok vydání: 2004
Předmět:
Zdroj: Molecular immunology. 42(10)
ISSN: 0161-5890
Popis: A basic glycoprotein oxiagin with molecular mass of 49.8 kDa was isolated from the venom of Central Asian cobra Naja oxiana. Partial amino acid sequence determination has shown that oxiagin belongs to reprolysins, a subfamily of animal metalloproteinases possessing a characteristic multidomain structure. Oxiagin was found to inhibit the classical pathway of the complement system. A study of the oxiagin influence on the different stages of the classical pathway showed that it inhibited the formation of C3-convertase. To achieve it, oxiagin binds to IgG on the surface of sheep erythrocytes sensitized with rabbit antibodies, thus, preventing the interaction of component C2 (without its inactivation) with immobilized C4b. IC50 for the inhibiton of classical pathway of complement system by oxiagin is 80 nM, while it does not affect the alternative pathway at concentrations up to 1.2 μM. Oxiagin possessed hemagglutinating activity towards sheep and rabbit erythrocytes, and this activity as well as the complement inhibition by oxiagin were suppressed by d -galactose. Oxiagin is the first representative of snake venom reprolysins that inhibits the complement system, utilizing non-proteolytic inhibiting strategy.
Databáze: OpenAIRE