1AGT

SOLUTION STRUCTURE OF THE POTASSIUM CHANNEL INHIBITOR AGITOXIN 2: CALIPER FOR PROBING CHANNEL GEOMETRY

Summary for 1AGT

• Entry DOI: 10.2210/pdb1agt/pdb
• Descriptor: AGITOXIN 2 (1 entity in total)
• Functional Keywords: potassium channel blocker, neurotoxin
• Biological source: Leiurus quinquestriatus hebraeus
• Cellular location: Secreted : P46111
• Total number of polymer chains: 1
• Total formula weight: 4104.98

Authors

Krezel, A.M.,Kasibhatla, C.,Hidalgo, P.,Mackinnon, R.,Wagner, G. (deposition date: 1995-04-14, release date: 1995-07-10, Last modification date: 2024-11-20)

Primary citation

Krezel, A.M.,Kasibhatla, C.,Hidalgo, P.,MacKinnon, R.,Wagner, G.
Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry.
Protein Sci., 4:1478-1489, 1995

PubMed Abstract: The structure of the potassium channel blocker agitoxin 2 was solved by solution NMR methods. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form the core of the molecule. One edge of the beta-sheet and the adjacent face of the helix form the interface with the Shaker K+ channel. The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins. However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. The rigid toxin molecule can be used to estimate dimensions of the potassium channel. Surface-exposed residues, Arg24, Lys27, and Arg31 of the beta-sheet, have been identified from mutagenesis studies as functionally important for blocking the Shaker K+ channel. The sequential and spatial locations of Arg24 and Arg31 are not conserved among the homologous toxins. Knowledge on the details of the channel-binding sites of agitoxin 2 formed a basis for site-directed mutagenesis studies of the toxin and the K+ channel sequences. Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions.

PubMed: 8520473

Experimental method

SOLUTION NMR