9JWL

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

Summary for 9JWL

• Entry DOI: 10.2210/pdb9jwl/pdb
• Descriptor: MSD1-holo chainA, beta-D-allopyranose (3 entities in total)
• Functional Keywords: de novo designed d-allose binding protein based on 1rpj, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 62327.16

Authors

Wang, X.,Liu, Y. (deposition date: 2024-10-10, release date: 2025-10-15, Last modification date: 2025-12-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)