4LLW

Crystal structure of Pertuzumab Clambda Fab with variable domain redesign (VRD2) at 1.95A

4LLW の概要

• エントリーDOI: 10.2210/pdb4llw/pdb
• 関連するPDBエントリー: 4LLD 4LLM 4LLQ 4LLU 4LLY
• 分子名称: mutated Pertuzumab Fab heavy chain, light chain Clambda, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: fab, 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: 95476.10

構造登録者

Pustilnik, A.,Lewis, S.M.,Wu, X.,Sereno, A.,Huang, F.,Guntas, G.,Leaver-Fay, A.,Smith, E.M.,Ho, C.,Hansen-Estruch, C.,Chamberlain, A.K.,Truhlar, S.M.,Kuhlman, B.,Demarest, S.J.,Atwell, S. (登録日: 2013-07-09, 公開日: 2014-01-29, 最終更新日: 2024-11-06)

主引用文献

Lewis, S.M.,Wu, X.,Pustilnik, A.,Sereno, A.,Huang, F.,Rick, H.L.,Guntas, G.,Leaver-Fay, A.,Smith, E.M.,Ho, C.,Hansen-Estruch, C.,Chamberlain, A.K.,Truhlar, S.M.,Conner, E.M.,Atwell, S.,Kuhlman, B.,Demarest, S.J.
Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.
Nat.Biotechnol., 32:191-198, 2014

PubMed Abstract: Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.

PubMed: 24463572
DOI: 10.1038/nbt.2797

実験手法

X-RAY DIFFRACTION (1.95 Å)