Crystal and Molecular Structure of S-Deoxo[Ile3]amaninamide: A Synthetic Analogue of Amanita Toxins

G. Shoham*, W. N. Lipscomb, D. C. Rees, G. Zanotti, Th Wieland

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The crystal structure of S-deoxo[Ile3] amaninamide, a nontoxic synthetic derivative of the Amanita phalloides mushroom toxins (amatoxins), has been determined by single-crystal X-ray diffraction. The crystals are monoclinic, space group P21, with 2 formula units per unit cell. Cell dimensions are a = 12.147 Å, b = 11.250 Å,c = 19.267 Å, and β = 92.41°. The structure was determined by molecular replacement methods and refined by least-squares techniques to a final R value of 0.065 for 3894 independent observations. Six intramolecular hydrogen bonds hold the bicyclic octapeptide in a compact conformation, which is very similar to the conformation of the naturally occurring (and toxic) amatoxin, β-amanitin. The study demonstrates that the 30-fold reduction in binding affinity to RNA polymerase B of the title amatoxin, and probably of most of the other amatoxin analogues with altered side chain 3, is not due to alteration of backbone conformation. The three water molecules and two ethanol molecules, crystallized with the amatoxin, form a strong and extensive intermolecular hydrogen-bonding system.

Original languageAmerican English
Pages (from-to)4606-4615
Number of pages10
JournalJournal of the American Chemical Society
Volume106
Issue number16
DOIs
StatePublished - 1 Aug 1984
Externally publishedYes

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