6T9E

Crystal structure of a bispecific DutaFab in complex with human PDGF

これはPDB形式変換不可エントリーです。

6T9E の概要

• エントリーDOI: 10.2210/pdb6t9e/pdb
• 分子名称: DutaFab mat VH chain, DutaFab mat VL chain, Platelet-derived growth factor subunit B (3 entities in total)
• 機能のキーワード: monoclonal antibody, bispecific antibody, fab fragment, pdgf, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 119478.50

構造登録者

Kimbung, R.,Logan, D.T.,Beckmann, R.,Jensen, K.,Speck, J.,Fenn, S.,Kettenberger, H. (登録日: 2019-10-28, 公開日: 2020-12-16, 最終更新日: 2024-10-16)

主引用文献

Beckmann, R.,Jensen, K.,Fenn, S.,Speck, J.,Krause, K.,Meier, A.,Roth, M.,Fauser, S.,Kimbung, R.,Logan, D.T.,Steegmaier, M.,Kettenberger, H.
DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously.
Nat Commun, 12:708-708, 2021

PubMed Abstract: We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, LCDR3 and HCDR2. Both paratopes can be independently selected and combined into the desired bispecific DutaFabs in a modular manner. X-ray crystal structures illustrate that DutaFabs are able to bind two target molecules simultaneously at the same Fv region comprising a VH-VL heterodimer. In the present study, this platform is applied to generate DutaFabs specific for VEGFA and PDGF-BB, which show high affinities, physico-chemical stability and solubility, as well as superior efficacy over anti-VEGF monotherapy in vivo. These molecules exemplify the usefulness of DutaFabs as a distinct class of antibody therapeutics, which is currently being evaluated in patients.

PubMed: 33514724
DOI: 10.1038/s41467-021-20949-3

実験手法

X-RAY DIFFRACTION (2.989 Å)