9JWT

De novo designed D-allose binding protein based on 1rpj

9JWT の概要

• エントリーDOI: 10.2210/pdb9jwt/pdb
• 分子名称: MSD3-holo, beta-D-allopyranose (3 entities in total)
• 機能のキーワード: de novo designed d-allose binding protein based on 1rpj, 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: 31041.44

構造登録者

Wang, X.,Liu, Y. (登録日: 2024-10-10, 公開日: 2025-10-15, 最終更新日: 2025-12-31)

主引用文献

Liu, Y.,Wu, R.,Wang, X.,Wang, S.,Chen, L.,Li, F.,Chen, Q.,Liu, H.
Enhancing functional proteins through multimodal inverse folding with ABACUS-T.
Nat Commun, 16:10177-10177, 2025

PubMed Abstract: Structure-based sequence redesign or inverse folding can significantly enhance structural stability but often compromises functional activity when performed using existing models. Here, we introduce ABACUS-T, a multimodal inverse folding model that improves precision and minimizes functional loss. ABACUS-T unifies several important features into one framework: detailed atomic sidechains and ligand interactions, a pre-trained protein language model, multiple backbone conformational states, and evolutionary information from multiple sequence alignment (MSA). Redesigned proteins show notable improvements: an allose binding protein achieves 17-fold higher affinity while retaining conformational change; redesigned endo-1,4-β-xylanase and TEM β-lactamase maintain or surpass wild-type activity; and OXA β-lactamase gains altered substrate selectivity. All achieve substantially increase thermostability (∆T ≥ 10 °C). In each test case, these enhancements are achieved by testing only a few sequences, each containing dozens of simultaneously mutated residues. ABACUS-T thus offers a promising tool for reengineering functional proteins in biotechnological applications.

PubMed: 41261139
DOI: 10.1038/s41467-025-65175-3

実験手法

X-RAY DIFFRACTION (1.6 Å)