1L6X

FC FRAGMENT OF RITUXIMAB BOUND TO A MINIMIZED VERSION OF THE B-DOMAIN FROM PROTEIN A CALLED Z34C

1L6X の概要

• エントリーDOI: 10.2210/pdb1l6x/pdb
• 関連するPDBエントリー: 1DN2
• 分子名称: IMMUNOGLOBULIN GAMMA-1 HEAVY CHAIN CONSTANT REGION, Minimized B-domain of Protein A Z34C, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: igg1 fc, protein a, fc complex, b-domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29525.91

構造登録者

Idusogie, E.E.,Presta, L.G.,Santoro-Gazzano, H.,Totpal, K.,Wong, P.Y.,Ultsch, M.,Meng, Y.G.,Mullkerrin, M.G. (登録日: 2002-03-14, 公開日: 2002-04-10, 最終更新日: 2024-10-16)

主引用文献

Idusogie, E.E.,Presta, L.G.,Gazzano-Santoro, H.,Totpal, K.,Wong, P.Y.,Ultsch, M.,Meng, Y.G.,Mulkerrin, M.G.
Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc.
J.Immunol., 164:4178-4184, 2000

PubMed Abstract: Rituxan (Rituximab) is a chimeric mAb with human IgG1 constant domains used in the therapy of non-Hodgkin's B cell lymphomas. This Ab targets B cells by binding to the cell-surface receptor, CD20. In our investigation of the mechanism of B cell depletion mediated by Rituximab, we first constructed mutants of Rituximab defective in complement activation but with all other effector functions intact. Our results demonstrate that the previously described C1q binding motif in murine IgG2b constituting residues E318, K320, and K322 is not applicable to a human IgG1 when challenged with either human, rabbit, or guinea pig complement. Alanine substitution at positions E318 and K320 in Rituximab had little or no effect on C1q binding and complement activation, whereas alanine substitution at positions D270, K322, P329, and P331 significantly reduced the ability of Rituximab to bind C1q and activate complement. We have also observed that concentrations of complement approaching physiological levels are able to rescue >60% of the activity of these mutant Abs with low affinity for C1q. These data localize the C1q binding epicenter on human IgG1 and suggest that there are species-specific differences in the C1q binding site of Igs.

PubMed: 10754313

実験手法

X-RAY DIFFRACTION (1.65 Å)