STRUCTURAL STUDIES ON JACALIN Ð CARBOHYDRATE COMPLEXES
K. Sekar,a
A. A. Jeyaprakash,b P. G. Rani,b
S. Katiyar,b A. Surolia,b and M. Vijayanb
aBioinformatics Centre and Supercomputer
Education and Research Centre; bMolecular Biophysics Unit, Indian Institute of
Science, Bangalore 560 012, India (sekar@physics.iisc.ernet.in)
Jacalin is a 66kDa tetrameric lectin
from the seeds of jackfruit (Artocarpus integrifolia). Each subunit consists of two chains, a long a chain and a short b chain,
produced by post-translational proteolysis. The structure of the lectin-bound
to Me-a-galactose was earlier solved in this
laboratory. The structure revealed a novel lectin fold and the use of
post-translational modification as a strategy for generating specificity for
galactose at the primary binding site. At the disaccharide level, it is
specific to tumour-related Galb1-3GalNAc,
known as T-antigen. We have now prepared and solved the structures of the
complexes of the lectin with Gal, Me-a-GalNAc, T-antigen, Me-a-T-antigen and GalNAcb1-3Gal-O-Me. In the
complexes with T-antigen and Me-a-T-antigen, the primary site is occupied by the GalNac residue.
The interactions of the Gal residue with the protein are confined to
water bridges. The methyl group in
Me-a-T-antigen has favourable interaction
with an aromatic residue, accounting for its increased affinity to the
lectin. In the complex with GalNAcb1-3Gal-O-Me, however, the primary site is occupied by the Gal
residue presumably on account of the favourable interaction of the methyl group
with the residue. The structures
of the complexes provide a reasonable explanation for the available
thermodynamic data of jacalin-carbohydrate interactions. The details will be presented.