8VEJ

De novo designed cholic acid binder: CHD_buttress

8VEJ の概要

• エントリーDOI: 10.2210/pdb8vej/pdb
• 分子名称: CHD_buttress, CHOLIC ACID (2 entities in total)
• 機能のキーワード: de novo designed protein, cholic acid, small molecule binder, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55766.08

構造登録者

Bera, A.K.,Tran, L.,Kang, A.,Baker, D. (登録日: 2023-12-19, 公開日: 2024-07-17, 最終更新日: 2024-07-31)

主引用文献

An, L.,Said, M.,Tran, L.,Majumder, S.,Goreshnik, I.,Lee, G.R.,Juergens, D.,Dauparas, J.,Anishchenko, I.,Coventry, B.,Bera, A.K.,Kang, A.,Levine, P.M.,Alvarez, V.,Pillai, A.,Norn, C.,Feldman, D.,Zorine, D.,Hicks, D.R.,Li, X.,Sanchez, M.G.,Vafeados, D.K.,Salveson, P.J.,Vorobieva, A.A.,Baker, D.
Binding and sensing diverse small molecules using shape-complementary pseudocycles.
Science, 385:276-282, 2024

PubMed Abstract: We describe an approach for designing high-affinity small molecule-binding proteins poised for downstream sensing. We use deep learning-generated pseudocycles with repeating structural units surrounding central binding pockets with widely varying shapes that depend on the geometry and number of the repeat units. We dock small molecules of interest into the most shape complementary of these pseudocycles, design the interaction surfaces for high binding affinity, and experimentally screen to identify designs with the highest affinity. We obtain binders to four diverse molecules, including the polar and flexible methotrexate and thyroxine. Taking advantage of the modular repeat structure and central binding pockets, we construct chemically induced dimerization systems and low-noise nanopore sensors by splitting designs into domains that reassemble upon ligand addition.

PubMed: 39024436
DOI: 10.1126/science.adn3780

実験手法

X-RAY DIFFRACTION (3.59 Å)