1agt

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

spinqualitylabelsall models 1agt Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1agt is a 1 chain structure with sequence from Leiurus hebraeus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 17 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KAX32_LEIHE Potent inhibitor of the Shaker potassium channels and its mammalian homologs (Kv1.1/KCNA1, Kv1.3/KCNA3, Kv1.6/KCNA6) (Ki<1 nM for all channels) (PubMed:20007782, PubMed:8204618). Also blocks Kv1.2/KCNA2 (IC(50)=26.8 nM) (PubMed:20007782, PubMed:8204618). It also shows a weak interaction with nicotinic acetylcholine receptors (nAChR), suggesting it may weakly inhibit it (PubMed:31276191). 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 PubMed 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. Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry.,Krezel AM, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G Protein Sci. 1995 Aug;4(8):1478-89. PMID:8520473 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Potassium channel toxin 3D structures

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