3G6A

Crystal structure of anti-IL-13 antibody CNTO607

3G6A の概要

• エントリーDOI: 10.2210/pdb3g6a/pdb
• 関連するPDBエントリー: 3G6D
• 分子名称: CNTO607 Fab Light chain, CNTO607 Fab Heavy chain (3 entities in total)
• 機能のキーワード: il-13, antibody, fab, monoclonal antibody, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94162.26

構造登録者

Teplyakov, A.,Obmolova, G.,Gilliland, G.L. (登録日: 2009-02-06, 公開日: 2009-04-28, 最終更新日: 2024-10-30)

主引用文献

Teplyakov, A.,Obmolova, G.,Wu, S.J.,Luo, J.,Kang, J.,O'Neil, K.,Gilliland, G.L.
Epitope mapping of anti-interleukin-13 neutralizing antibody CNTO607.
J.Mol.Biol., 389:115-123, 2009

PubMed Abstract: CNTO607 is a neutralizing anti-interleukin-13 (IL-13) human monoclonal antibody obtained from a phage display library. To determine how this antibody inhibits the biological effect of IL-13, we determined the binding epitope by X-ray crystallography. The crystal structure of the complex between CNTO607 Fab and IL-13 reveals the antibody epitope at the surface formed by helices A and D of IL-13. This epitope overlaps with the IL-4Ralpha/IL-13Ralpha1 receptor-binding site, which explains the neutralizing effect of CNTO607. The extensive antibody interface covers an area of 1000 A(2), which is consistent with the high binding affinity. The key features of the interface are the charge and shape complementarity of the molecules that include two hydrophobic pockets on IL-13 that accommodate Phe32 [complementarity-determining region (CDR) L2] and Trp100a (CDR H3) and a number of salt bridges between basic residues of IL-13 and acidic residues of the antibody. Comparison with the structure of the free Fab shows that the CDR residues do not change their conformation upon complex formation, with the exception of two residues in CDR H3, Trp100a and Asp100b, which change rotamer conformations. To evaluate the relative contribution of the epitope residues to CNTO607 binding, we performed alanine-scanning mutagenesis of the A-D region of IL-13. This study confirmed the primary role of electrostatic interactions for antigen recognition.

PubMed: 19361524
DOI: 10.1016/j.jmb.2009.03.076

実験手法

X-RAY DIFFRACTION (2.1 Å)