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AGKISTROTOXIN, A PHOSPHOLIPASE A2-TYPE PRESYNAPTIC NEUROTOXIN FROM AGKISTRODON HALYS PALLAS
Structural highlights
FunctionPA2N_GLOHA Snake venom phospholipase A2 (PLA2) that inhibits neuromuscular transmission by blocking acetylcholine release from the nerve termini. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe crystal structure of agkistrodotoxin containing eight copies of molecules in the asymmetric unit has been determined at 2.8 A resolution to a crystallographic R factor of 0.207 by the molecular replacement technique. Two spatially adjacent regions of agkistrodotoxin molecule, turn 55-61 and stretch 85-91, are remarkably different from those of non-neurotoxic isoforms in conformation and electrostatic characteristics. These regions are likely to be involved in the recognition of agkistrodotoxin towards the specific receptor at the presynaptic membrane. The structural comparison of the interfacial recognition site with non-neurotoxic isoforms reveals a decreased hydrophobicity and lack of residues with bulky hydrophobic side-chains (i.e. Trp) to serve as membrane anchors. This structural feature of agkistrodotoxin may be related to the reduced non-specific binding of the toxin to non-targeted membrane before it arrives at the presynaptic membrane and recognizes the putative receptor. A unique hydrophobic patch including residues I19, P20, F21, A23, F24, M118 and F119 is found on the surface of the molecule near the entrance of the hydrophobic channel which plays an important role in crystal packing. The interaction mode between the patches might give a clue to the binding of the neurotoxin on the membrane. The agkistrodotoxin molecules in the asymmetric unit form two tetramers and each tetramer exhibits a novel "dimer of dimers"-like structure. A molecule-spanning four-stranded antiparallel beta-sheet is formed by the beta-wings of two molecules within a tetramer. Crystal structure of agkistrodotoxin, a phospholipase A2-type presynaptic neurotoxin from agkistrodon halys pallas.,Tang L, Zhou YC, Lin ZJ J Mol Biol. 1998 Sep 11;282(1):1-11. PMID:9733637[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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