1mtx › Citations

Determination of the three-dimensional structure of margatoxin by 1H, 13C, 15N triple-resonance nuclear magnetic resonance spectroscopy.

Johnson BA, Stevens SP, Williamson JM
Biochemistry 33 15061-70 (1994)
Cited: 48 times
EuropePMC logo PMID: 7999764

Abstract

The solution structure of the 39-residue peptide margatoxin, a scorpion toxin that selectively blocks the voltage-gated potassium-channel Kv1.3, has been determined by NMR spectroscopy. The toxin was isotopically labeled with 13C and 15N and studied using two-dimensional homonuclear and three- and four-dimensional heteronuclear NMR spectroscopy. The final structure was determined using 501 constraints, comprising 422 NOE constraints, 60 dihedral angle constraints, 9 disulfide constraints, and 10 hydrogen bond constraints. Structures were initially determined with the program PEGASUS and subsequently refined with X-PLOR. The average rms deviation from a calculated average structure for the backbone atoms of residues 3-38 is 0.40 A. A helix is present from residues 11 to 20 and includes two proline residues at positions 15 and 16. A loop at residues 21-24 leads into a two-strand antiparallel sheet from residues 25 to 38 with a turn at residues 30-33. Residues 3-6 run adjacent to the 33-38 strand but do not form a canonical beta-strand. The two additional residues of margatoxin, relative to the related toxins charybdotoxin and iberiotoxin, insert in a manner that extends the beta-sheet by one residue. Otherwise, the global structure is very similar to that of these two other toxins. The longer sheet may have implications for channel selectivity.

Reviews - 1mtx mentioned but not cited (3)

  1. Computational methods of studying the binding of toxins from venomous animals to biological ion channels: theory and applications. Gordon D, Chen R, Chung SH. Physiol Rev 93 767-802 (2013)
  2. Computational Studies of Venom Peptides Targeting Potassium Channels. Chen R, Chung SH. Toxins (Basel) 7 5194-5211 (2015)
  3. Overview of protein structural and functional folds. Sun PD, Foster CE, Boyington JC. Curr Protoc Protein Sci Chapter 17 Unit 17.1 (2004)

Articles - 1mtx mentioned but not cited (7)

  1. Computational simulations of interactions of scorpion toxins with the voltage-gated potassium ion channel. Yu K, Fu W, Liu H, Luo X, Chen KX, Ding J, Shen J, Jiang H. Biophys J 86 3542-3555 (2004)
  2. Recombinant expression of margatoxin and agitoxin-2 in Pichia pastoris: an efficient method for production of KV1.3 channel blockers. Anangi R, Koshy S, Huq R, Beeton C, Chuang WJ, King GF. PLoS One 7 e52965 (2012)
  3. Motions and structural variability within toxins: implication for their use as scaffolds for protein engineering. Gilquin B, Bourgoin M, Ménez R, Le Du MH, Servent D, Zinn-Justin S, Ménez A. Protein Sci 12 266-277 (2003)
  4. Binding modes of two scorpion toxins to the voltage-gated potassium channel kv1.3 revealed from molecular dynamics. Chen R, Chung SH. Toxins (Basel) 6 2149-2161 (2014)
  5. Modeling of the Binding of Peptide Blockers to Voltage-Gated Potassium Channels: Approaches and Evidence. Novoseletsky VN, Volyntseva AD, Shaitan KV, Kirpichnikov MP, Feofanov AV. Acta Naturae 8 35-46 (2016)
  6. Molecular Dynamics Simulation Reveals Specific Interaction Sites between Scorpion Toxins and Kv1.2 Channel: Implications for Design of Highly Selective Drugs. Yuan S, Gao B, Zhu S. Toxins (Basel) 9 (2017)
  7. GFP-Margatoxin, a Genetically Encoded Fluorescent Ligand to Probe Affinity of Kv1.3 Channel Blockers. Denisova KR, Orlov NA, Yakimov SA, Kryukova EA, Dolgikh DA, Kirpichnikov MP, Feofanov AV, Nekrasova OV. Int J Mol Sci 23 1724 (2022)


Reviews citing this publication (7)

  1. Therapeutic potential of venom peptides. Lewis RJ, Garcia ML. Nat Rev Drug Discov 2 790-802 (2003)
  2. The charybdotoxin family of K+ channel-blocking peptides. Miller C. Neuron 15 5-10 (1995)
  3. Potassium channels: from scorpion venoms to high-resolution structure. Garcia ML, Gao Y, McManus OB, Kaczorowski GJ. Toxicon 39 739-748 (2001)
  4. Potassium channels in T lymphocytes: toxins to therapeutic immunosuppressants. Chandy KG, Cahalan M, Pennington M, Norton RS, Wulff H, Gutman GA. Toxicon 39 1269-1276 (2001)
  5. Novel miniproteins engineered by the transfer of active sites to small natural scaffolds. Vita C, Vizzavona J, Drakopoulou E, Zinn-Justin S, Gilquin B, Ménez A. Biopolymers 47 93-100 (1998)
  6. Treating autoimmune disorders with venom-derived peptides. Shen B, Cao Z, Li W, Sabatier JM, Wu Y. Expert Opin Biol Ther 17 1065-1075 (2017)
  7. Developing methylotrophic microbial platforms for a methanol-based bioindustry. Singh HB, Kang MK, Kwon M, Kim SW. Front Bioeng Biotechnol 10 1050740 (2022)

Articles citing this publication (31)

  1. Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins. Aiyar J, Withka JM, Rizzi JP, Singleton DH, Andrews GC, Lin W, Boyd J, Hanson DC, Simon M, Dethlefs B. Neuron 15 1169-1181 (1995)
  2. c-Abl phosphorylates α-synuclein and regulates its degradation: implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson's disease. Mahul-Mellier AL, Fauvet B, Gysbers A, Dikiy I, Oueslati A, Georgeon S, Lamontanara AJ, Bisquertt A, Eliezer D, Masliah E, Halliday G, Hantschel O, Lashuel HA. Hum Mol Genet 23 2858-2879 (2014)
  3. Letter Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone. Tudor JE, Pallaghy PK, Pennington MW, Norton RS. Nat Struct Biol 3 317-320 (1996)
  4. Determination of the three-dimensional solution structure of Raphanus sativus antifungal protein 1 by 1H NMR. Fant F, Vranken W, Broekaert W, Borremans F. J Mol Biol 279 257-270 (1998)
  5. kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity. Srinivasan KN, Sivaraja V, Huys I, Sasaki T, Cheng B, Kumar TK, Sato K, Tytgat J, Yu C, San BC, Ranganathan S, Bowie HJ, Kini RM, Gopalakrishnakone P. J Biol Chem 277 30040-30047 (2002)
  6. 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 4 1478-1489 (1995)
  7. Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus, with high affinity for voltage-gated potassium channels. Blanc E, Sabatier JM, Kharrat R, Meunier S, el Ayeb M, Van Rietschoten J, Darbon H. Proteins 29 321-333 (1997)
  8. Changing the structural context of a functional beta-hairpin. Synthesis and characterization of a chimera containing the curaremimetic loop of a snake toxin in the scorpion alpha/beta scaffold. Drakopoulou E, Zinn-Justin S, Guenneugues M, Gilqin B, Ménez A, Vita C. J Biol Chem 271 11979-11987 (1996)
  9. The three-dimensional solution structure of Aesculus hippocastanum antimicrobial protein 1 determined by 1H nuclear magnetic resonance. Fant F, Vranken WF, Borremans FA. Proteins 37 388-403 (1999)
  10. FRET in Membrane Biophysics: An Overview. Loura LM, Prieto M. Front Physiol 2 82 (2011)
  11. Scorpion toxins: tools for studying K+ channels. Garcia ML, Hanner M, Kaczorowski GJ. Toxicon 36 1641-1650 (1998)
  12. Structural and functional implications of a proline residue in the antimicrobial peptide gaegurin. Suh JY, Lee YT, Park CB, Lee KH, Kim SC, Choi BS. Eur J Biochem 266 665-674 (1999)
  13. Isolation and characterization of a novel lepidopteran-selective toxin from the venom of South Indian red scorpion, Mesobuthus tamulus. Wudayagiri R, Inceoglu B, Herrmann R, Derbel M, Choudary PV, Hammock BD. BMC Biochem 2 16 (2001)
  14. 1H-NMR-derived secondary structure and the overall fold of the potent anti-mammal and anti-insect toxin III from the scorpion Leiurus quinquestriatus quinquestriatus. Landon C, Cornet B, Bonmatin JM, Kopeyan C, Rochat H, Vovelle F, Ptak M. Eur J Biochem 236 395-404 (1996)
  15. Refined solution structure of the anti-mammal and anti-insect LqqIII scorpion toxin: comparison with other scorpion toxins. Landon C, Sodano P, Cornet B, Bonmatin JM, Kopeyan C, Rochat H, Vovelle F, Ptak M. Proteins 28 360-374 (1997)
  16. Solution structure of TsKapa, a charybdotoxin-like scorpion toxin from Tityus serrulatus with high affinity for apamin-sensitive Ca(2+)-activated K+ channels. Blanc E, Lecomte C, Rietschoten JV, Sabatier JM, Darbon H. Proteins 29 359-369 (1997)
  17. Purification and characterization of a novel short-chain insecticidal toxin with two disulfide bridges from the venom of the scorpion Liocheles australasiae. Matsushita N, Miyashita M, Sakai A, Nakagawa Y, Miyagawa H. Toxicon 50 861-867 (2007)
  18. Characterization of PO1, a new peptide ligand of the apamin-sensitive Ca2+ activated K+ channel. Zerrouk H, Laraba-Djebari F, Fremont V, Meki A, Darbon H, Mansuelle P, Oughideni R, van Rietschoten J, Rochat H, Martin-Eauclaire MF. Int J Pept Protein Res 48 514-521 (1996)
  19. A novel short-chain peptide BmKX from the Chinese scorpion Buthus martensi Karsch, sequencing, gene cloning and structure determination. Wang CG, Cai Z, Lu W, Wu J, Xu Y, Shi Y, Chi CW. Toxicon 45 309-319 (2005)
  20. Novel alpha-KTx sites in the BK channel and comparative sequence analysis reveal distinguishing features of the BK and KV channel outer pore. Giangiacomo KM, Becker J, Garsky C, Schmalhofer W, Garcia ML, Mullmann TJ. Cell Biochem Biophys 52 47-58 (2008)
  21. Solution structure of a K(+)-channel blocker from the scorpion Tityus cambridgei. Wang I, Wu SH, Chang HK, Shieh RC, Yu HM, Chen C. Protein Sci 11 390-400 (2002)
  22. Solution structure of potassium channel-inhibiting scorpion toxin Lq2. Renisio JG, Lu Z, Blanc E, Jin W, Lewis JH, Bornet O, Darbon H. Proteins 34 417-426 (1999)
  23. BTK-2, a new inhibitor of the Kv1.1 potassium channel purified from Indian scorpion Buthus tamulus. Dhawan R, Varshney A, Mathew MK, Lala AK. FEBS Lett 539 7-13 (2003)
  24. MR spectroscopy in sinus mucocele: N-acetyl mimics of brain N-acetylaspartate. Andre E, Xu M, Yang D, Siow JK, Yeo TT, Xu Y, Lim CC. AJNR Am J Neuroradiol 27 2210-2213 (2006)
  25. NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the metallo-ribozyme ribonuclease P. Koutmou KS, Casiano-Negroni A, Getz MM, Pazicni S, Andrews AJ, Penner-Hahn JE, Al-Hashimi HM, Fierke CA. Proc Natl Acad Sci U S A 107 2479-2484 (2010)
  26. Maurotoxin and the Kv1.1 channel: voltage-dependent binding upon enantiomerization of the scorpion toxin disulfide bridge Cys31-Cys34. Lecomte C, Ben Khalifa R, Martin-Eauclaire MF, Kharrat R, El Ayeb M, Darbon H, Rochat H, Crest M, Sabatier JM. J Pept Res 55 246-254 (2000)
  27. Margatoxin-bound quantum dots as a novel inhibitor of the voltage-gated ion channel Kv1.3. Schwartz AB, Kapur A, Wang W, Huang Z, Fardone E, Palui G, Mattoussi H, Fadool DA. J Neurochem 140 404-420 (2017)
  28. Observation of noncovalent complexes between margatoxin and the Kv1.3 peptide ligands: A model investigation using ion-spray mass spectrometry. Bakhtiarcor R, Bednarek MA. J Am Soc Mass Spectrom 7 1075-1080 (1996)
  29. Olfactory bulb-targeted quantum dot (QD) bioconjugate and Kv1.3 blocking peptide improve metabolic health in obese male mice. Schwartz AB, Kapur A, Huang Z, Anangi R, Spear JM, Stagg S, Fardone E, Dekan Z, Rosenberg JT, Grant SC, King GF, Mattoussi H, Fadool DA. J Neurochem 157 1876-1896 (2021)
  30. Optimization of Pichia pastoris Expression System for High-Level Production of Margatoxin. Naseem MU, Tajti G, Gaspar A, Szanto TG, Borrego J, Panyi G. Front Pharmacol 12 733610 (2021)
  31. Scorpion toxins prefer salt solutions. Nikouee A, Khabiri M, Cwiklik L. J Mol Model 21 287 (2015)


Quick links