5VH4

Crystal structure of Fab fragment of anti-TNFa antibody infliximab in an I-centered orthorhombic crystal form

5VH4 の概要

• エントリーDOI: 10.2210/pdb5vh4/pdb
• 関連するPDBエントリー: 5VH3 5VH5
• 分子名称: Infliximab Fab Heavy Chain, Infliximab Fab Light Chain, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: antibody, fab, biosimilar, infliximab, tnfa, anti-tnfa, immune system
• 由来する生物種: Mus musculus, Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97271.29

構造登録者

Mayclin, S.J.,Edwards, T.E.,Lerch, T.F.,Conlan, H.,Sharpe, P. (登録日: 2017-04-12, 公開日: 2017-05-03, 最終更新日: 2024-10-23)

主引用文献

Lerch, T.F.,Sharpe, P.,Mayclin, S.J.,Edwards, T.E.,Lee, E.,Conlon, H.D.,Polleck, S.,Rouse, J.C.,Luo, Y.,Zou, Q.
Infliximab crystal structures reveal insights into self-association.
MAbs, 9:874-883, 2017

PubMed Abstract: Aggregation and self-association in protein-based biotherapeutics are critical quality attributes that are tightly controlled by the manufacturing process. Aggregates have the potential to elicit immune reactions, including neutralizing anti-drug antibodies, which can diminish the drug's efficacy upon subsequent dosing. The structural basis of reversible self-association, a form of non-covalent aggregation in the native state, is only beginning to emerge for many biologics and is often unique to a given molecule. In the present study, crystal structures of the infliximab (Remicade) Fc and Fab domains were determined. The Fab domain structures are the first to be reported in the absence of the antigen (i.e., tumor necrosis factor), and are consistent with a mostly rigid complementarity-determining region loop structure and rotational flexibility between variable and constant regions. A potential self-association interface is conserved in two distinct crystal forms of the Fab domain, and solution studies further demonstrate that reversible self-association of infliximab is mediated by the Fab domain. The crystal structures and corresponding solution studies help rationalize the propensity for infliximab to self-associate and provide insights for the design of improved control strategies in biotherapeutics development.

PubMed: 28421849
DOI: 10.1080/19420862.2017.1320463

実験手法

X-RAY DIFFRACTION (2 Å)