9qup

Tb(III)-bound de novo protein scaffold TFD-EE MPNN

spinqualitylabelsall models 9qup, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9qup is a 2 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: EDO, GOL, NA, TB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Incorporating metal cofactors into computationally designed protein scaffolds provides a versatile route to novel protein functions, including the potential for new-to-nature enzyme catalysis. However, a major challenge in protein design is to understand how the scaffold architecture influences conformational dynamics. Here, we characterized structure and dynamics of a modular de novo scaffold with flexible inter-domain linkers. Three rationally engineered variants with different metal specificity were studied by combining X-ray crystallography, NMR spectroscopy, and molecular dynamics simulations. The lanthanide-binding variant was initially trapped in an inactive conformational state, which impaired efficient metal coordination and cerium-dependent photocatalytic activity. Stabilization of the active conformation by AI-guided sequence optimization using ProteinMPNN led to accelerated lanthanide binding and a 10-fold increase in k(cat)/K(m) for a photoenzymatic model reaction. Our results suggest that modular scaffold architectures provide an attractive starting point for de novo metalloenzyme engineering and that ProteinMPNN-based sequence redesign can stabilize desired conformational states. Modular protein scaffold architecture and AI-guided sequence optimization facilitate de novo metalloenzyme engineering.,Wagner Egea P, Delhommel F, Mustafa G, Leiss-Maier F, Klimper L, Badmann T, Heider A, Wille I, Groll M, Sattler M, Zeymer C Structure. 2025 Nov 5:S0969-2126(25)00397-1. doi: 10.1016/j.str.2025.10.010. PMID:41197620 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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