ArticleProceedings of the National Academy of Sciences of the United States of America2004
Mimicking enzyme evolution by generating new (betaalpha)8-barrels from (betaalpha)4-half-barrels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Designing de novo TIM barrels: insights into stabilization, diversification, and functionalization strategies.Biochemical Society transactions · 2026Review
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stepwise introduction of stabilizing mutations reveals nonlinear additive effects in de novo TIM barrels.Protein science : a publication of the Protein Society · 2024Article
- Functionalization of a symmetric protein scaffold: Redundant folding nuclei and alternative oligomeric folding pathways.Protein science : a publication of the Protein Society · 2022Article
- A newly introduced salt bridge cluster improves structural and biophysical properties of de novo TIM barrels.Protein science : a publication of the Protein Society · 2022Article
- What Have We Learned from Design of Function in Large Proteins?Biodesign research · 2022Review
- Variable and Conserved Regions of Secondary Structure in the β-Trefoil Fold: Structure Versus Function.Frontiers in molecular biosciences · 2022Article
- The Stability Landscape of de novo TIM Barrels Explored by a Modular Design Approach.Journal of molecular biology · 2021Article
- Evolution, folding, and design of TIM barrels and related proteins.Current opinion in structural biology · 2021Review
- The AbDesign computational pipeline for modular backbone assembly and design of binders and enzymes.Protein science : a publication of the Protein Society · 2021Article
- Identification and Analysis of Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design.Journal of molecular biology · 2020Article
- Reconstructing the Remote Origins of a Fold Singleton from a Flavodoxin-Like Ancestor.Biochemistry · 2019Article
- Extent and Origins of Functional Diversity in a Subfamily of Glycoside Hydrolases.Journal of molecular biology · 2019Article
- Activity and Thermostability of GH5 Endoglucanase Chimeras from Mesophilic and Thermophilic Parents.Applied and environmental microbiology · 2019Article
- Highly active enzymes by automated combinatorial backbone assembly and sequence design.Nature communications · 2018Article
- Article
- Evolution of a protein folding nucleus.Protein science : a publication of the Protein Society · 2016Article
- Artificial domain duplication replicates evolutionary history of ketol-acid reductoisomerases.Protein science : a publication of the Protein Society · 2016Article
- Why reinvent the wheel? Building new proteins based on ready-made parts.Protein science : a publication of the Protein Society · 2016Review
- De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy.Nature chemical biology · 2016Article
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3 authors.
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Abstract
Gene duplication and fusion events that multiply and link functional protein domains are crucial mechanisms of enzyme evolution. The analysis of amino acid sequences and three-dimensional structures suggested that the (betaalpha)8-barrel, which is the most frequent fold among enzymes, has evolved by the duplication, fusion, and mixing of (betaalpha)4-half-barrel domains. Here, we mimicked this evolutionary strategy by generating in vitro (betaalpha)8-barrels from (betaalpha)4-half-barrels that were deduced from the enzymes imidazole glycerol phosphate synthase (HisF) and N'[(5'-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide isomerase (HisA). To this end, the gene for the C-terminal (betaalpha)4-half-barrel (HisF-C) of HisF was duplicated and fused in tandem to yield HisF-CC, which is more stable than HisF-C. In the next step, by optimizing side-chain interactions within the center of the beta-barrel of HisF-CC, the monomeric and compact (betaalpha)8-barrel protein HisF-C*C was generated. Moreover, the genes for the N- and C-terminal (betaalpha)4-half-barrels of HisF and HisA were fused crosswise to yield the chimeric proteins HisFA and HisAF. Whereas HisFA contains native secondary structure elements but adopts ill-defined association states, the (betaalpha)8-barrel HisAF is a stable and compact monomer that reversibly unfolds with high cooperativity. The results obtained suggest a previously undescribed dimension for the diversification of enzymatic activities: new (betaalpha)8-barrels with novel functions might have evolved by the exchange of (betaalpha)4-half-barrel domains with distinct functional properties.
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