Structure-Function Analysis and Insights into the Reduced Toxicity of Abrus precatorius Agglutinin I in Relation to Abrin

Abstract

Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that ϳ200 -2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate.

A monoclonal antibody to an abrin chimera recognizing a unique epitope on abrin A chain confers protection from abrin-induced lethality

“…Studies to determine the reactivity of mAb A7C4 to the RIPs abrin and APA demonstrated that in spite of 67% sequence identity between ABA and APAA, 16 the core epitope of mAb A7C4 is restricted to amino acid sequence unique to abrin A chain within 1-123 amino acids. Moreover, mAb A7C4 did not bind to the chimeric construct ABA …”

“…Though ABA and APAA share 67% sequence identity, 16 the observation that mAb A7C4 does not recognize the sequence of APAA suggests that the core epitope comprises majorly of the amino acid sequences that are unique to ABA only. The absence of binding to the construct APA 1-123 ABA (Fig.…”

Simultaneous quantification of five bacterial and plant toxins from complex matrices using a multiplexed fluorescent magnetic suspension assay

“…For ricin, the oral toxicity in humans expressed as half-maximal lethal dose (LD50) is estimated to be 1-20 mg/kg body weight and for abrin 0.1-1 mg/kg body weight.3,4 Both R. communis and A. precatorius seeds contain a second toxic lectin named R. communis agglutinin and A. precatorius agglutinin, which are highly homologous (around 90% sequence identity for ricin and R. communis agglutinin) to ricin or abrin, respectively, but are less toxic. [5][6][7] of cholinergic neurons to induce flaccid paralysis by interfering with components of the vesicle fusion machinery. Exceedingly small quantities of toxin are sufficient for poisoning: the oral lethal dose of botulinum toxin for man is approximately 1 mg/kg.8 Staphylococcal enterotoxin B (SEB) is one of several heatstable enterotoxins produced by the Gram-positive bacterium Staphylococcus aureus, which is known as a major human pathogen.…”

Phytochemical Analysis and Chemical Fingerprinting of Seeds of Abrus Precatorius L.

“…Seeds of Abrus precatorius L. are among the most poisonous seeds in the world and contain principle compound, abrine, abrin A, abrin B, abrin C abricin and abridin 12 . The present work deals with phytochemical analysis and chemical fingerprinting of important medicinal plant, Abrus precatorius L.…”