Molecular pharmacology of plant lectins: Studies on ricin and concanavalin A (NSC 143504)

A. P. Grollman, C. Grunfeld, C. F. Brewer, D. M. Marcus

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

A toxic protein, isolated and purified from extracts of Ricinus communis, inhibits protein synthesis in HeLa cells and cell free lysates prepared from rabbit reticulocytes. The effect on HeLa cells occurs only after a significant delay and can be partially or completely blocked by adding lactose. Low concentrations of ricin cause dissociation of polyribosomes in HeLa cells; this effect parallels inhibition of protein synthesis. Dissociation can be prevented by adding anisomycin, an inhibitor of peptide bond formation. In separate experiments, binding of α methyl D glucopyranoside (uniformly enriched with 14% 13C) to concanavalin A was studied by pulsed Fourier transform carbon magnetic resonance techniques. The spin lattice relaxation time for each of the 13C atoms of the sugar was measured in the absence and presence of zinc and manganese derivatives of concanavalin A, and the contribution of the paramagnetic manganese ion to the relaxation times of the bound saccharide was determined. These data permit calculation of the distances between the ion and the individual carbon atoms and determine the three dimensional orientation of the sugar relative to the transition metal site in concanavalin A. The results indicate that the sugar binds in the Cl chair conformation with its 3 and 4 carbons closest to the manganese ion at a mean distance of 10 Å. This magnetic resonance method may be used to determine the geometry of complexes formed between various small molecules, including drugs, and macromolecules that contain a binding site for paramagnetic ions.

Original languageEnglish (US)
Pages (from-to)491-501
Number of pages11
JournalCANCER CHEMOTHER.REP.
Volume58 I
Issue number4
StatePublished - 1974
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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