Myotoxin

from Wikipedia, the free encyclopedia
Three-dimensional structure of crotamine , a myotoxin that acts on sodium channels , according to PDB 1H5O . The cysteines that form disulfide bridges have been highlighted.

Myotoxin (from ancient Greek μῦς mys , gen. Μυός myos 'muscle' and τοξίνη , ancient Greek pronounced toxíne 'the poisonous substance', collectively muscle poison ) is a snake poison - peptide with a muscle paralyzing and muscle-destroying function. In the venom of the rattlesnakes ( Crotalus ), in particular, there are various homologous peptides that have this function.

history

Crotalus durissus terrificus (shower rattlesnake)

The Brazilian scientist José Moura Gonçalves purified and identified in the 1950s the first Myotoxin, Crotamin , from the venom of Neotropical rattlesnake (Crotalus durissus terrificus) , a tropical rattlesnake that in South America is home.

Structure and function

Structurally very similar myotoxins - all of them are small, basic peptides with molecular masses around 4.5 kDa, isoelectric points (pI) around 9.8 and structurally stabilized by three disulfide bridges - are present in the venom of pit vipers and vipers . The myotoxins lead to muscle paralysis ( myotoxicity ) in prey and prevent them from escaping. Death occurs within minutes through paralysis of abdominal breathing and another non-enzymatic mechanism that leads to local death of muscle tissue ( myonecrosis ).

Sequence homology

Myotoxins from various snake venoms were isolated and characterized primarily in the 1960s to 1980s. The comparison of their amino acid sequences shows a high degree of sequence homology and the conservative maintenance of the three cystines (six cysteines that form three disulfide bridges: Cys4-Cys36, Cys11-Cys30 and Cys18-Cys37), which stabilize the structure of the myosin molecule ( yellow: cysteine; green: conservatively homologous (identical) amino acid sequence):

designation
 Amino acid sequence ( single letter code ) Species ( Crotalus )
Crotamine YK Q C HKK G GH C FPK EK I C L PPSSD F GKMD C RW R WK CC KK GSG C. durissus terrificus
Myotoxin I. YK R C HKK E GH C FPK TV I C L PPSSD F GKMD C RW K WK CC KK GSVN C. viridis concolor
Myotoxin II YK R C HKK G GH C FPK EK I C T PPSSD F GKMD C RW K WK CC KK GSVN C. viridis concolor
Myotoxin II m. YK R C HKK G GH C FPK TV I C L PPSSD F GKMD C RW R WK CC KK GSVN C. viridis concolor
Peptide c YK R C HKK G GH C FPK TV I C L PPSSD F GKMD C RW K WK CC KK SVN C. viridis helleri
Myotoxin a YK Q C HKK G GH C FPK EK I C I PPSSD L GKMD C RW K WK CC KK GSG C. viridis viridis
CAM YK R C HKK G GH C FPK TV I C L PPSSD F GKMD C RW R WK CC KK GSVNN C. adamanteus

Individual evidence

  1. ↑ G. Nicastro, L. Franzoni, C. de Chiara, AC Mancin, JR Giglio, A. Spisni Solution structure of crotamine, a Na + channel affecting toxin from Crotalus durissus terrificus venom (PDF; 472 kB), In: Eur J Biochem 270 (9), pp. 1969-1979 (2003). PMID 12709056 .
  2. ^ PR Griffin, SD Aird A new small myotoxin from the venom of the prairie rattlesnake (Crotalus viridis viridis) . In: FEBS Lett ., Vol. 274, pp. 43-47 (1990). PMID 2253781 .
  3. ^ Y. Samejima, Y. Aoki, D. Mebs Amino acid sequence of a myotoxin from venom of the eastern diamondback rattlesnake (Crotalus adamanteus) . In: Toxicon , Vol. 29, pp. 461-468 (1991). PMID 1862521 .
  4. ↑ V. Fadel, P. Bettendorff, T. Herrmann, WF de Azevedo Jr., EB Oliveira, T. Yamane and K. Wüthrich Automated NMR structure determination and disulfide bond identification of the myotoxin crotamine from Crotalus durissus terrificus . In: Toxicon (2005) 1; 46 (7): 759-767. PMID 16185738 .
  5. ↑ JC Laure The primary structure of crotamine . In: Hoppe Seylers Z Physiol Chem (1975), Volume 246, pp. 799-803. doi : 10.1515 / bchm2.1975.356.1.213
  6. ↑ a b c A. L. Bieber, RH McParland and RR Becker Amino acid sequences of myotoxins from "Crotalus viridis concolor" venom . In: Toxicon (1987), Vol. 25, pp. 677-680. PMID 3629618 .
  7. ↑ N. Maeda and N. Tamiya Some chemical properties of the venom of the rattlesnake, "Crotalus viridis helleri" . In: Toxicon (1978), vol. 16, pp. 431-441. PMID 694946 .
  8. ↑ JW Fox, M. Elzinga and AT Tu Amino acid sequence and disulfide bond assignment of myotoxin a isolated from the venom of prairie rattlesnake ("Crotalus viridis viridis") . In: Biochemistry (1979), vol. 18, pp. 678-684. PMID 570412 .
  9. ↑ Y. Samejima, Y. Aoki and D. Mebs Structural studies on a myotoxin from "Crotalus adamanteus" venom in Progress in Venom and Toxin Research (1988), pp. 186–187, P. Gopalakkrishnakone and CK Tan (eds.) , Natl. Univ. Singapore Press, Singapore.

literature

  • Alan L. Harvey (Ed.): Snake Toxins , International Encyclopedia of Pharmacology and Therapeutics, Sect. 134, Pergamon Press, New York, Oxford, Beijing, Frankfurt, São Paulo, Sydney, Tokyo, Toronto 1991, pp. 70–71 (general), pp. 118–119 (mechanism), pp. 120–121 (structure / Activity); Pp. 394-395 (cloning); P. 435 (sequences).