1A2A

AGKISTROTOXIN, A PHOSPHOLIPASE A2-TYPE PRESYNAPTIC NEUROTOXIN FROM AGKISTRODON HALYS PALLAS

Summary for 1A2A

• Entry DOI: 10.2210/pdb1a2a/pdb
• Descriptor: PHOSPHOLIPASE A2, CHLORIDE ION (2 entities in total)
• Functional Keywords: presynaptic neurotoxin, phospholipase a2, hydrolase, lipid degradation
• Biological source: Gloydius halys (halys viper)
• Cellular location: Secreted: P14421
• Total number of polymer chains: 8
• Total formula weight: 111106.31

Authors

Tang, L.,Zhou, Y.,Lin, Z. (deposition date: 1997-12-25, release date: 1999-01-13, Last modification date: 2024-10-30)

Primary citation

Tang, L.,Zhou, Y.C.,Lin, Z.J.
Crystal structure of agkistrodotoxin, a phospholipase A2-type presynaptic neurotoxin from agkistrodon halys pallas.
J.Mol.Biol., 282:1-11, 1998

PubMed Abstract: The 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.

PubMed: 9733637
DOI: 10.1006/jmbi.1998.1987

Experimental method

X-RAY DIFFRACTION (2.8 Å)