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1NIY

THREE DIMENSIONAL SOLUTION STRUCTURE OF HAINANTOXIN-IV BY 2D 1H-NMR

Summary for 1NIY
Entry DOI10.2210/pdb1niy/pdb
NMR InformationBMRB: 5674
DescriptorHAINANTOXIN-IV (1 entity in total)
Functional Keywordsneurotoxin, inhibitor cystine knot motif, toxin
Biological sourceOrnithoctonus hainana
Total number of polymer chains1
Total formula weight3999.63
Authors
Li, D.,Lu, S.,Gu, X.,Liang, S. (deposition date: 2002-12-30, release date: 2003-01-14, Last modification date: 2024-10-30)
Primary citationLi, D.,Xiao, Y.,Xu, X.,Xiong, X.,Lu, S.,Liu, Z.,Zhu, Q.,Wang, M.,Gu, X.,Liang, S.
Structure-Activity Relationships of Hainantoxin-IV and Structure Determination of Active and Inactive Sodium Channel Blockers.
J.Biol.Chem., 279:37734-37740, 2004
Cited by
PubMed Abstract: 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.
PubMed: 15201273
DOI: 10.1074/jbc.M405765200
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

226707

數據於2024-10-30公開中

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