Inhibitors of PLA2 neurotoxins from the serum of Australian snakes

Main participants: S. Sekuloski, R. Dunn, and KW Broady [P. Hains, B. Nield, M. Padula, A. Tseng]

Progress to date: A group of snake serum proteins have been identified which inhibit the PLA2 neurotoxins from a range of Australian and foreign snakes. One of these proteins, NSI from the tiger snake, Notechis scutatus has been purified and has undergone extensive structural and functional investigation. The investigation of these inhibitor proteins was the subject of a R&D Syndicate Research Program aimed at developing therapeutic control of PLA2s involved in inflammatory diseases. Homologous inhibitors have been identified in most Australian elapid snakes and the genes encoding the inhibitors [both alpha and beta chains] from the Mainland tiger snake [N.scutatus], Tasmanian tiger snake [N.ater], Coastal Taipan [Oxyuranus scutellatus], Inland Taipan [O.microlepidotus] and Eastern brown snake [Pseudonaja textilis] have been cloned and several chains expressed in the Baculovirus expression system.

Funding sources: UTS Internal grant, PLA2 Inhibitor R&D Syndicate

Publications:

Thurn, M.J., Broady, K.W. and P.J. Mirtschin. Neutralisation of Tiger snake (Notechis scutatus) venom by serum from other Australian elapids. Toxicon. 31(7), 909 (1993)

S.Y. Lau (1992) BSc (Hons) Thesis, UTS

P. Hains (1993) BSc (Hons) Thesis, UTS

B. Nield (1997) BSc (Hons) Thesis, UTS

P. Hains (1998) PhD Thesis, UTS

PG Hains, A Tseng and KW Broady (2000) Purification and characterisation of phospholipase A2 inhibitors from Australian elapid sera. Biochem.J. 346(1), 139-146.

PG Hains, KL Sung, A Tseng and KW Broady (2000) Functional characteristics of a phospholipase A2 inhibitor from Notechis ater serum. J Biol. Chem 275(2), 983-991.

Dunn RD and Broady KW (2001) Snake inhibitors of phospholipase A2 enzymes [review]. Biochimica et Biophysica Acta, 55803, 1-9.

Hains PG, Neild B, Sekuloski S, Dunn R and Broady KW (2001) Sequencing and two dimensional structure prediction of a phospholipase A2 inhibitor from the serum of the Common tiger snake (Notechis scutatus). Journal of Molecular Biology 312(4), 875-884.