1ryg | pdb_00001ryg

Three dimensional solution structure of the R29A MUTANT of sodium channels inhibitor HAINANTOXIN-IV by 2D 1H-NMR

spinqualitylabelsall models 1ryg, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ryg is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: NH2 Related: 1niy, 1ryv Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed Hainantoxin-IV (HNTX-IV) can specifically inhibit the neuronal tetrodotoxin-sensitive sodium channels and defines a new class of depressant spider toxin. The sequence of native HNTX-IV is ECLGFGKGCNPSNDQCCKSSNLVCSRKHRWCKYEI-NH(2). In the present study, to obtain further insight into the primary and tertiary structural requirements of neuronal sodium channel blockers, we determined the solution structure of HNTX-IV as a typical inhibitor cystine knot motif and synthesized four mutants designed based on the predicted sites followed by structural elucidation of two inactive mutants. Pharmacological studies indicated that the S12A and R26A mutants had activities near that of native HNTX-IV, while K27A and R29A demonstrated activities reduced by 2 orders of magnitude. (1)H MR analysis showed the similar molecular conformations for native HNTX-IV and four synthetic mutants. Furthermore, in the determined structures of K27A and R29A, the side chains of residues 27 and 29 were located in the identical spatial position to those of native HNTX-IV. These results suggested that residues Ser(12), Arg(26), Lys(27), and Arg(29) were not responsible for stabilizing the distinct conformation of HNTX-IV, but Lys(27) and Arg(29) were critical for the bioactivities. The potency reductions produced by Ala substitutions were primarily due to the direct interaction of the essential residues Lys(27) and Arg(29) with sodium channels rather than to a conformational change. After comparison of these structures and activities with correlated toxins, we hypothesized that residues Lys(27), Arg(29), His(28), Lys(32), Phe(5), and Trp(30) clustered on one face of HNTX-IV were responsible for ligand binding. Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers.,Li D, Xiao Y, Xu X, Xiong X, Lu S, Liu Z, Zhu Q, Wang M, Gu X, Liang S J Biol Chem. 2004 Sep 3;279(36):37734-40. Epub 2004 Jun 16. PMID:15201273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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