1IQW

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

Summary for 1IQW

• Entry DOI: 10.2210/pdb1iqw/pdb
• Descriptor: ANTIBODY M-HFE7A, LIGHT CHAIN, ANTIBODY M-HFE7A, HEAVY CHAIN (3 entities in total)
• Functional Keywords: immunoglobulin, fab, anti_fas, agonistic antibody, apoptosis, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 48806.03

Authors

Ito, S.,Takayama, T.,Hanzawa, H.,Ichikawa, K.,Ohsumi, J.,Serizawa, N.,Hata, T.,Haruyama, H. (deposition date: 2001-08-10, release date: 2002-01-23, Last modification date: 2024-10-30)

Primary citation

Ito, S.,Takayama, T.,Hanzawa, H.,Ichikawa, K.,Ohsumi, J.,Serizawa, N.,Hata, T.,Haruyama, H.
Crystal structure of the antigen-binding fragment of apoptosis-inducing mouse anti-human Fas monoclonal antibody HFE7A.
J.Biochem., 131:137-143, 2002

PubMed Abstract: 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.

PubMed: 11754745
DOI: 10.1093/oxfordjournals.jbchem.a003068

Experimental method

X-RAY DIFFRACTION (2.5 Å)