1jnn

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Revision as of 07:27, 18 November 2007

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spinqualitylabelsall models 1jnn, resolution 3.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Fab-Estradiol Complexes

Overview

Subtle modulation of antibody-binding properties by protein engineering, often lies with an accurate structural and energetic description of how an, antigen is recognised. Thus, with the intent to increase the affinity and, add a bias in favour of natural estradiol compared with its chemically, modified immunogen, we have determined the crystal structure of two, anti-estradiol monoclonal antibodies, 10G6D6 and 17E12E5. Although, generated against the same estradiol derivative, these antibodies share, little sequence identity, which is reflected in dissimilar binding pockets, and in different positioning of the steroid. In both antibodies the, characteristic 17-hydroxyl group is buried deeply at the bottom of, hydrophobic pockets and stabilised by hydrogen bonds. Apart from this, similarity, the steroid is oriented differently in the respective binding, pockets. The high specificity of both antibodies has been mapped out, and, even closely related steroids show low cross-reactivity. The structural, studies of the complex formed between 10G6D6 and 6-CMO-estradiol have, identified contacts between the 6-CMO coupling linker and an arginine, residue from the heavy chain CDR2 segment. This segment is now being, targeted by random mutagenesis to select mutants with a preference for, natural estradiol compared to the branched hapten.

About this Structure

1JNN is a Protein complex structure of sequences from Mus musculus with EST as ligand. Full crystallographic information is available from OCA.

Reference

Highly specific anti-estradiol antibodies: structural characterisation and binding diversity., Monnet C, Bettsworth F, Stura EA, Le Du MH, Menez R, Derrien L, Zinn-Justin S, Gilquin B, Sibai G, Battail-Poirot N, Jolivet M, Menez A, Arnaud M, Ducancel F, Charbonnier JB, J Mol Biol. 2002 Jan 25;315(4):699-712. PMID:11812141

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