8BL9

Crystal Structure of Sam0.7

8BL9 の概要

• エントリーDOI: 10.2210/pdb8bl9/pdb
• 分子名称: Sam0.7 (2 entities in total)
• 機能のキーワード: protein design, vegf inhibitor, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16718.01

構造登録者

Maksymenko, K.,ElGamacy, M.,Hartmann, M.D. (登録日: 2022-11-09, 公開日: 2024-05-22, 最終更新日: 2025-12-10)

主引用文献

Maksymenko, K.,Hatskovska, V.,Coles, M.,Aghaallaei, N.,Pashkovskaia, N.,Borbaran-Bravo, N.,Pilz, M.,Bucher, P.,Volz, M.,Pereira, J.,Hartmann, M.D.,Tabatabai, G.,Feucht, J.,Liebau, S.,Muller, P.,Lupas, A.N.,Skokowa, J.,ElGamacy, M.
A Complementarity-Based Approach to De Novo Binder Design.
Adv Sci, 12:e02015-e02015, 2025

PubMed Abstract: De novo design of binders capable of targeting arbitrarily selected epitopes remains a substantial challenge. Here, a generalizable computational strategy is presented to design site-specific protein binders, obviating steps of extensive empirical optimization or in vitro screening. The dock-and-design pipeline retrieves complementary scaffolds from a protein structure database to a given query epitope, where the scaffold is mutated to carve a binding site de novo. The docking step utilizes a novel fingerprint that greatly simplifies and accelerates the surface complementarity evaluation. As proof-of-concept, we designed protein binders to target three distinct epitopes on two different oncogenic targets; vascular endothelial growth factor (VEGF) and interleukin-7 receptor-α (IL-7Rα). Experimental characterization of only 24 candidates identified nanomolar binders against each of the target epitopes, where the binders belonged to five different folds. Several designs were active in vitro. Moreover, anti-VEGF designs showed tumor-inhibiting activity in vivo, highlighting their therapeutic potential.

PubMed: 40686280
DOI: 10.1002/advs.202502015

実験手法

X-RAY DIFFRACTION (1.8 Å)