7Q4Q

Magacizumab Fab fragment in complex with human LRG1 epitope

7Q4Q の概要

• エントリーDOI: 10.2210/pdb7q4q/pdb
• 分子名称: Magacizumab light chain, Magacizumab heavy chain, LRG1 epitope, ... (5 entities in total)
• 機能のキーワード: antibody, cancer, angiogenesis, human, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 98470.00

構造登録者

Gutierrez-Fernandez, J.,Luecke, H. (登録日: 2021-11-01, 公開日: 2022-06-15, 最終更新日: 2024-10-23)

主引用文献

Gutierrez-Fernandez, J.,Javaid, F.,De Rossi, G.,Chudasama, V.,Greenwood, J.,Moss, S.E.,Luecke, H.
Structural basis of human LRG1 recognition by Magacizumab, a humanized monoclonal antibody with therapeutic potential.
Acta Crystallogr D Struct Biol, 78:725-734, 2022

PubMed Abstract: The formation of new dysfunctional blood vessels is a crucial stage in the development of various conditions such as macular degeneration, diabetes, cardiovascular disease, neurological disease and inflammatory disorders, as well as during tumor growth, eventually contributing to metastasis. An important factor involved in pathogenic angiogenesis is leucine-rich α-2-glycoprotein 1 (LRG1), the antibody blockade of which has been shown to lead to a reduction in both choroidal neovascularization and tumor growth in mouse models. In this work, the structural interactions between the LRG1 epitope and the Fab fragment of Magacizumab, a humanized function-blocking IgG4 against LRG1, are analysed, determining its specific binding mode and the key residues involved in LRG1 recognition. Based on these structural findings, a series of mutations are suggested that could be introduced into Magacizumab to increase its affinity for LRG1, as well as a model of the entire Fab-LRG1 complex that could enlighten new strategies to enhance affinity, consequently leading towards an even more efficient therapeutic.

PubMed: 35647920
DOI: 10.1107/S2059798322004132

実験手法

X-RAY DIFFRACTION (1.65 Å)