1iqw

From Proteopedia

Revision as of 14:03, 15 February 2008

CRYSTAL STRUCTURE OF THE FAB FRAGMENT OF THE MOUSE ANTI-HUMAN FAS ANTIBODY HFE7A

Overview

Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system, plays important roles in many biological processes, including the, elimination of autoreactive lymphoid cells. The mouse anti-human Fas, monoclonal antibody HFE7A (m-HFE7A), which induces apoptosis, has been, humanized based on a structure predicted by homology modeling. A version, of humanized HFE7A is currently under development for the treatment of, autoimmune diseases such as rheumatoid arthritis. For a deeper, understanding of the protein engineering aspect of antibody humanization, for which information on the three-dimensional structure is essential, we, determined the crystal structure of the m-HFE7A antigen-binding fragment, (Fab) by X-ray crystallography at 2.5 A resolution. The main-chain, conformation of the five loops in the six complementarity-determining, regions (CDRs) was correctly predicted with root-mean-square deviations of, 0.30-1.04 A based on a comparison of the crystal structure with the, predicted structure. The CDR-H3 conformation of the crystal structure, which was not classified as one of the canonical structures, was, completely different from that of the predicted structure but adopted the, conformation which followed the "H3-rules." The results of charge, distribution analysis of the antigen-binding site suggest that, electrostatic interactions may be important for its binding to Fas.

About this Structure

1IQW is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

Reference

Crystal structure of the antigen-binding fragment of apoptosis-inducing mouse anti-human Fas monoclonal antibody HFE7A., Ito S, Takayama T, Hanzawa H, Ichikawa K, Ohsumi J, Serizawa N, Hata T, Haruyama H, J Biochem (Tokyo). 2002 Jan;131(1):137-43. PMID:11754745

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