1oaw Citations

Three-dimensional solution structure of the calcium channel antagonist omega-agatoxin IVA: consensus molecular folding of calcium channel blockers.

J. Mol. Biol. 250 659-71 (1995)
Cited: 41 times
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The three-dimensional solution structure of omega-agatoxin IVA, which is a specific blocker of the P-type calcium channel isolated from funnel web spider venom and has a molecular mass of 5.2 kDa, was determined by two dimensional 1H NMR spectroscopy, combined with simulated annealing calculations. On the basis of 563 experimental constraints, including 516 distance constraints obtained from the nuclear Overhauser effect, 21 torsion angle (phi, chi 1) constraints, and 26 constraints associated with hydrogen bonds and disulfide bonds, a total of 14 converged structures were obtained. The atomic root mean square difference for the 14 converged structures with respect to the mean coordinates is 0.42 (+/- 0.07) A for the backbone atoms (N, C alpha, C) and 0.95 (+/- 0.15) A for all heavy atoms of the central part (residues 4 to 38) constrained by four disulfide bonds. The N- and C-terminal segments (residues 1 to 3 and 39 to 48, respectively) have a disordered structure in aqueous solution. The molecular structure of omega-agatoxin IVA is composed of a short triple-stranded antiparallel beta-sheet, three loops, and the disordered N- and C-terminal segments. The overall beta-sheet topology is +2x, -1, which is the same as that reported for omega-conotoxin GVIA, an N-type calcium channel blocker. Irrespective of differences in the number of disulfide bonds and low primary sequence homology, these two peptide toxins show a significant structural similarity in three dimensions. The whole-cell voltage-clamp recording using rat cerebellar slices suggests that the hydrophobic C-terminal segment of omega-agatoxin IVA, which does not exist in omega-conotoxin GVIA, plays a crucial role in the blocking action of omega-agatoxin IVA on the P-type calcium channel in rat cerebellar Purkinje cells. The present study provides a molecular basis for the toxin-channel interaction, and thereby provides insight into the discrimination of different subtypes of calcium channels.

Articles - 1oaw mentioned but not cited (3)

Reviews citing this publication (13)

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  9. Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel. Nicholson GM, Little MJ, Birinyi-Strachan LC. Toxicon 43 587-599 (2004)
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  2. The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider. Fletcher JI, Smith R, O'Donoghue SI, Nilges M, Connor M, Howden ME, Christie MJ, King GF. Nat. Struct. Biol. 4 559-566 (1997)
  3. Functional conversion of hemocyanin to phenoloxidase by horseshoe crab antimicrobial peptides. Nagai T, Osaki T, Kawabata S. J. Biol. Chem. 276 27166-27170 (2001)
  4. A new fold in the scorpion toxin family, associated with an activity on a ryanodine-sensitive calcium channel. Mosbah A, Kharrat R, Fajloun Z, Renisio JG, Blanc E, Sabatier JM, El Ayeb M, Darbon H. Proteins 40 436-442 (2000)
  5. Structure-function studies of omega-atracotoxin, a potent antagonist of insect voltage-gated calcium channels. Wang X, Smith R, Fletcher JI, Wilson H, Wood CJ, Howden ME, King GF. Eur. J. Biochem. 264 488-494 (1999)
  6. A hot spot for the interaction of gating modifier toxins with voltage-dependent ion channels. Winterfield JR, Swartz KJ. J. Gen. Physiol. 116 637-644 (2000)
  7. Discovery and structure of a potent and highly specific blocker of insect calcium channels. Wang XH, Connor M, Wilson D, Wilson HI, Nicholson GM, Smith R, Shaw D, Mackay JP, Alewood PF, Christie MJ, King GF. J Biol Chem 276 40306-40312 (2001)
  8. Structure and sodium channel activity of an excitatory I1-superfamily conotoxin. Buczek O, Wei D, Babon JJ, Yang X, Fiedler B, Chen P, Yoshikami D, Olivera BM, Bulaj G, Norton RS. Biochemistry 46 9929-9940 (2007)
  9. Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus. Pallaghy PK, Alewood D, Alewood PF, Norton RS. FEBS Lett. 419 191-196 (1997)
  10. Electrophysiological characterization and molecular identification of the Phoneutria nigriventer peptide toxin PnTx2-6. Matavel A, Cruz JS, Penaforte CL, Araújo DA, Kalapothakis E, Prado VF, Diniz CR, Cordeiro MN, Beirão PS. FEBS Lett. 523 219-223 (2002)
  11. Solution structure of the sodium channel antagonist conotoxin GS: a new molecular caliper for probing sodium channel geometry. Hill JM, Alewood PF, Craik DJ. Structure 5 571-583 (1997)
  12. The structure of spider toxin huwentoxin-II with unique disulfide linkage: evidence for structural evolution. Shu Q, Lu SY, Gu XC, Liang SP. Protein Sci. 11 245-252 (2002)
  13. Alpha-amylase inhibitors selected from a combinatorial library of a cellulose binding domain scaffold. Lehtiö J, Teeri TT, Nygren PA. Proteins 41 316-322 (2000)
  14. Solution structure of hpTX2, a toxin from Heteropoda venatoria spider that blocks Kv4.2 potassium channel. Bernard C, Legros C, Ferrat G, Bischoff U, Marquardt A, Pongs O, Darbon H. Protein Sci. 9 2059-2067 (2000)
  15. Molecular basis of the high-affinity activation of type 1 ryanodine receptors by imperatoxin A. Lee CW, Lee EH, Takeuchi K, Takahashi H, Shimada I, Sato K, Shin SY, Kim DH, Kim JI. Biochem. J. 377 385-394 (2004)
  16. Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel. Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I. J. Mol. Biol. 321 517-526 (2002)
  17. Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine. Gilquin B, Lecoq A, Desné F, Guenneugues M, Zinn-Justin S, Ménez A. Proteins 34 520-532 (1999)
  18. Adenosine A(1)-receptor-mediated tonic inhibition of glutamate release at rat hippocampal CA3-CA1 synapses is primarily due to inhibition of N-type Ca(2+) channels. Manita S, Kawamura Y, Sato K, Inoue M, Kudo Y, Miyakawa H. Eur. J. Pharmacol. 499 265-274 (2004)
  19. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging. Moore SJ, Leung CL, Norton HK, Cochran JR. PLoS ONE 8 e60498 (2013)
  20. High yield production and refolding of the double-knot toxin, an activator of TRPV1 channels. Bae C, Kalia J, Song I, Yu J, Kim HH, Swartz KJ, Kim JI. PLoS ONE 7 e51516 (2012)
  21. Circular dichroism spectra of calcium channel antagonist omega-conotoxins. Kim JI, Ohtake A, Sato K. Biochem. Biophys. Res. Commun. 230 133-135 (1997)
  22. Solution structure of agelenin, an insecticidal peptide isolated from the spider Agelena opulenta, and its structural similarities to insect-specific calcium channel inhibitors. Yamaji N, Sugase K, Nakajima T, Miki T, Wakamori M, Mori Y, Iwashita T. FEBS Lett. 581 3789-3794 (2007)
  23. Sequence-specific assignment of 1H-NMR resonance and determination of the secondary structure of Jingzhaotoxin-I. Zeng XZ, Zhu Q, Liang SP. Acta Biochim. Biophys. Sin. (Shanghai) 37 567-572 (2005)
  24. δ/ω-Plectoxin-Pt1a: an excitatory spider toxin with actions on both Ca(2+) and Na(+) channels. Zhou Y, Zhao M, Fields GB, Wu CF, Branton WD. PLoS ONE 8 e64324 (2013)
  25. 1H NMR study of robustoxin, the lethal neurotoxin from the funnel web spider Atrax robustus. Temple MD, Hinds MG, Sheumack DD, Howden ME, Norton RS. Toxicon 37 485-506 (1999)