ArticleProceedings of the National Academy of Sciences of the United States of America2020
Tight and specific lanthanide binding in a de novo TIM barrel with a large internal cavity designed by symmetric domain fusion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Design of a site selective heterochromic bimetallic lanthanide coiled coil with nanometre-scale control.Chemical science · 2026Article
- Customizing the structure of minimal TIM barrels to craft efficient de novo enzymes.Nature chemical biology · 2026Article
- Stability and cooperativity in chimeric de novo TIM barrels via quarter swapping.Protein science : a publication of the Protein Society · 2026Article
- Computational redesign and directed evolution of a lanthanide-dependent photoredox enzyme for enantioselective diol cleavage.Chemical science · 2026Article
- Designing de novo TIM barrels: insights into stabilization, diversification, and functionalization strategies.Biochemical Society transactions · 2026Review
- A Luminescence-Based Screening Platform for Lanthanide-Binding Peptides and Proteins.ACS chemical biology · 2025Article
- A cytokine-based designer enzyme with an abiological multinuclear metal center exhibits intrinsic and extrinsic catalysis.Nature communications · 2025Article
- Designing Enzymatic Reactivity with an Expanded Palette.Chembiochem : a European journal of chemical biology · 2025Review
- The structure of a NEMO construct engineered for screening reveals novel determinants of inhibition.Structure (London, England : 1993) · 2025Article
- Application of phage surface display for the identification of EuFrontiers in bioengineering and biotechnology · 2025Article
- A De Novo Metalloenzyme for Cerium Photoredox Catalysis.Journal of the American Chemical Society · 2024Article
- Spiers Memorial Lecture: Engineering biocatalysts.Faraday discussions · 2024Article
- Structure-driven development of a biomimetic rare earth artificial metalloprotein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- De novo design of buttressed loops for sculpting protein functions.Nature chemical biology · 2024Article
- Rare earth elements in biology: From biochemical curiosity to solutions for extractive industries.Microbial biotechnology · 2024Review
- Diversifying de novo TIM barrels by hallucination.Protein science : a publication of the Protein Society · 2024Article
- Mononuclear binding and catalytic activity of europium(III) and gadolinium(III) at the active site of the model metalloenzyme phosphotriesterase.Acta crystallographica. Section D, Structural biology · 2024Article
- Article
- Atomically Accurate Design of Metalloproteins with Predefined Coordination Geometries.Journal of the American Chemical Society · 2023Article
- Eu(III) and Cm(III) Complexation by the Aminocarboxylates NTA, EDTA, and EGTA Studied with NMR, TRLFS, and ITC-An Improved Approach to More Robust Thermodynamics.Molecules (Basel, Switzerland) · 2023Article
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9 authors.
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Abstract
De novo protein design has succeeded in generating a large variety of globular proteins, but the construction of protein scaffolds with cavities that could accommodate large signaling molecules, cofactors, and substrates remains an outstanding challenge. The long, often flexible loops that form such cavities in many natural proteins are difficult to precisely program and thus challenging for computational protein design. Here we describe an alternative approach to this problem. We fused two stable proteins with C2 symmetry-a de novo designed dimeric ferredoxin fold and a de novo designed TIM barrel-such that their symmetry axes are aligned to create scaffolds with large cavities that can serve as binding pockets or enzymatic reaction chambers. The crystal structures of two such designs confirm the presence of a 420 cubic Ångström chamber defined by the top of the designed TIM barrel and the bottom of the ferredoxin dimer. We functionalized the scaffold by installing a metal-binding site consisting of four glutamate residues close to the symmetry axis. The protein binds lanthanide ions with very high affinity as demonstrated by tryptophan-enhanced terbium luminescence. This approach can be extended to other metals and cofactors, making this scaffold a modular platform for the design of binding proteins and biocatalysts.
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