2q3n

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Template:STRUCTURE 2q3n

Agglutinin from Abrus Precatorius (APA-I)


Overview

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 approximately 200-2000-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.

About this Structure

2Q3N is a Protein complex structure of sequences from Abrus precatorius. This structure supersedes the now removed PDB entry 2amz. Full crystallographic information is available from OCA.

Reference

Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin., Bagaria A, Surendranath K, Ramagopal UA, Ramakumar S, Karande AA, J Biol Chem. 2006 Nov 10;281(45):34465-74. Epub 2006 Jun 13. PMID:16772301 Page seeded by OCA on Sun May 4 14:16:04 2008

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