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PDBsum entry 1vtx

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protein links
Neurotoxin PDB id
1vtx
Jmol
Contents
Protein chain
42 a.a. *
* Residue conservation analysis
PDB id:
1vtx
Name: Neurotoxin
Title: Delta-atracotoxin-hv1 (versutoxin) from hadronyche versuta, nmr, 20 structures
Structure: Delta-atracotoxin-hv1. Chain: a. Synonym: versutoxin
Source: Hadronyche versuta. Organism_taxid: 6904. Secretion: venom
NMR struc: 20 models
Authors: J.I.Fletcher,B.E.Chapman,G.F.King
Key ref:
J.I.Fletcher et al. (1997). The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel. Structure, 5, 1525-1535. PubMed id: 9384567 DOI: 10.1016/S0969-2126(97)00301-8
Date:
13-Mar-97     Release date:   28-Jan-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13494  (TXDT1_HADVE) -  Delta-hexatoxin-Hv1a
Seq:
Struc:
42 a.a.
42 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     pathogenesis   1 term 
  Biochemical function     sodium channel inhibitor activity     1 term  

 

 
DOI no: 10.1016/S0969-2126(97)00301-8 Structure 5:1525-1535 (1997)
PubMed id: 9384567  
 
 
The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel.
J.I.Fletcher, B.E.Chapman, J.P.Mackay, M.E.Howden, G.F.King.
 
  ABSTRACT  
 
BACKGROUND: Versutoxin (delta-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. delta-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; delta-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of delta-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. RESULTS: The solution structure of delta-ACTX-Hv1, determined using NMR spectroscopy, comprises a core beta region containing a triple-stranded antiparallel beta sheet, a thumb-like extension protruding from the beta region and a C-terminal 310 helix that is appended to the beta domain by virtue of a disulphide bond. The beta region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with mu-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, delta-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. CONCLUSIONS: delta-ACTX-Hv1 shows no structural homology with either sea anemone or alpha-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that delta-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and alpha-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. The b turns in d-ACTX-Hv1. Backbone N, Ca and C atoms are coloured purple, O atoms are in red, HN atoms are cyan, sidechains are magenta, and hydrogen bonds are represented as dotted green lines. (a) Classical type I b turn (Asn26-Gly29). (b) Type II b turn (Lys3-Asn6); the asparagine pseudo-turn, whereby the Asn6 Cb and Cgatoms geometrically mimic the backbone C and N atoms of a classical b turn and the Asn6 HD21 sidechain hydrogen forms a hydrogen bond with the Lys4 carbonyl oxygen, is apparent. (c) Type VIa1 b turn (Cys15-Met18), resulting from a Cys16-Pro17 cis peptide bond.
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1525-1535) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19592486 N.Yamaji, M.J.Little, H.Nishio, B.Billen, E.Villegas, Y.Nishiuchi, J.Tytgat, G.M.Nicholson, and G.Corzo (2009).
Synthesis, solution structure, and phylum selectivity of a spider delta-toxin that slows inactivation of specific voltage-gated sodium channel subtypes.
  J Biol Chem, 284, 24568-24582.  
18625007 S.J.Gunning, F.Maggio, M.J.Windley, S.M.Valenzuela, G.F.King, and G.M.Nicholson (2008).
The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels.
  FEBS J, 275, 4045-4059.  
18355315 Y.Han, F.Huang, H.Jiang, L.Liu, Q.Wang, Y.Wang, X.Shao, C.Chi, W.Du, and C.Wang (2008).
Purification and structural characterization of a D-amino acid-containing conopeptide, conomarphin, from Conus marmoreus.
  FEBS J, 275, 1976-1987.
PDB codes: 2jqc 2yyf
17092528 D.A.Hanck, and M.F.Sheets (2007).
Site-3 toxins and cardiac sodium channels.
  Toxicon, 49, 181-193.  
17268611 G.Estrada, E.Villegas, and G.Corzo (2007).
Spider venoms: a rich source of acylpolyamines and peptides as new leads for CNS drugs.
  Nat Prod Rep, 24, 145-161.  
17696362 O.Buczek, D.Wei, J.J.Babon, X.Yang, B.Fiedler, P.Chen, D.Yoshikami, B.M.Olivera, G.Bulaj, and R.S.Norton (2007).
Structure and sodium channel activity of an excitatory I1-superfamily conotoxin.
  Biochemistry, 46, 9929-9940.
PDB codes: 2jry 2p4l
17192003 S.P.Sarma, G.S.Kumar, S.Sudarslal, P.Iengar, P.Ramasamy, S.K.Sikdar, K.S.Krishnan, and P.Balaram (2005).
Solution structure of delta-Am2766: a highly hydrophobic delta-conotoxin from Conus amadis that inhibits inactivation of neuronal voltage-gated sodium channels.
  Chem Biodivers, 2, 535-556.  
14976206 L.Volpon, H.Lamthanh, J.Barbier, N.Gilles, J.Molgó, A.Ménez, and J.M.Lancelin (2004).
NMR solution structures of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels.
  J Biol Chem, 279, 21356-21366.
PDB codes: 1g1p 1g1z
14596608 D.Alewood, L.C.Birinyi-Strachan, P.K.Pallaghy, R.S.Norton, G.M.Nicholson, and P.F.Alewood (2003).
Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus).
  Biochemistry, 42, 12933-12940.  
14556622 L.Jouvensal, L.Quillien, E.Ferrasson, Y.Rahbé, J.Guéguen, and F.Vovelle (2003).
PA1b, an insecticidal protein extracted from pea seeds (Pisum sativum): 1H-2-D NMR study and molecular modeling.
  Biochemistry, 42, 11915-11923.
PDB code: 1p8b
12824480 P.Escoubas, C.Bernard, G.Lambeau, M.Lazdunski, and H.Darbon (2003).
Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels.
  Protein Sci, 12, 1332-1343.
PDB code: 1lmm
11874465 N.Gilles, G.Harrison, I.Karbat, M.Gurevitz, G.M.Nicholson, and D.Gordon (2002).
Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider delta-atracotoxin.
  Eur J Biochem, 269, 1500-1510.  
  11522785 X.H.Wang, M.Connor, D.Wilson, H.I.Wilson, G.M.Nicholson, R.Smith, D.Shaw, J.P.Mackay, P.F.Alewood, M.J.Christie, and G.F.King (2001).
Discovery and structure of a potent and highly specific blocker of insect calcium channels.
  J Biol Chem, 276, 40306-40312.
PDB codes: 1g9p 1hp3
11025543 J.Lehtiö, T.T.Teeri, and P.A.Nygren (2000).
Alpha-amylase inhibitors selected from a combinatorial library of a cellulose binding domain scaffold.
  Proteins, 41, 316-322.  
10607642 B.M.Olivera, L.J.Cruz, and D.Yoshikami (1999).
Effects of Conus peptides on the behavior of mice.
  Curr Opin Neurobiol, 9, 772-777.  
10491100 J.I.Fletcher, A.J.Dingley, R.Smith, M.Connor, M.J.Christie, and G.F.King (1999).
High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant polypeptide.
  Eur J Biochem, 264, 525-533.
PDB codes: 1c4e 2gur
10508777 P.J.Pereira, V.Lozanov, A.Patthy, R.Huber, W.Bode, S.Pongor, and S.Strobl (1999).
Specific inhibition of insect alpha-amylases: yellow meal worm alpha-amylase in complex with the amaranth alpha-amylase inhibitor at 2.0 A resolution.
  Structure, 7, 1079-1088.
PDB code: 1clv
9753689 D.A.Oren, O.Froy, E.Amit, N.Kleinberger-Doron, M.Gurevitz, and B.Shaanan (1998).
An excitatory scorpion toxin with a distinctive feature: an additional alpha helix at the C terminus and its implications for interaction with insect sodium channels.
  Structure, 6, 1095-1103.
PDB code: 1bcg
9765223 M.J.Little, C.Zappia, N.Gilles, M.Connor, M.I.Tyler, M.F.Martin-Eauclaire, D.Gordon, and G.M.Nicholson (1998).
delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels.
  J Biol Chem, 273, 27076-27083.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.