ArticleProceedings of the National Academy of Sciences of the United States of America2000
Directed evolution of a (beta alpha)8-barrel enzyme to catalyze related reactions in two different metabolic pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 169 citations in OpenAlex.
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- Functional shifts of the dual-substrate phosphoribosyl isomerase PriA from primary to specialized metabolism in rare Actinomycetota.Microbial genomics · 2026Article
- Retracing the Rapid Evolution of an Herbicide-Degrading Enzyme by Protein Engineering.ACS catalysis · 2023Article
- Enabling technology and core theory of synthetic biology.Science China. Life sciences · 2023Review
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- Directed Evolution Methods for Enzyme Engineering.Molecules (Basel, Switzerland) · 2021Review
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- The Role of Gene Elongation in the Evolution of Histidine Biosynthetic Genes.Microorganisms · 2020Article
- Mutational Pathways and Trade-Offs Between HisA and TrpF Functions: Implications for Evolution via Gene Duplication and Divergence.Frontiers in microbiology · 2020Article
- Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop.The Biochemical journal · 2016Article
- How special is the biochemical function of native proteins?F1000Research · 2016Review
- Long-Term Persistence of Bi-functionality Contributes to the Robustness of Microbial Life through Exaptation.PLoS genetics · 2016Article
- Two-step Ligand Binding in a (βα)8 Barrel Enzyme: SUBSTRATE-BOUND STRUCTURES SHED NEW LIGHT ON THE CATALYTIC CYCLE OF HisA.The Journal of biological chemistry · 2015Article
- On the role of physics and evolution in dictating protein structure and function.Israel journal of chemistry · 2014Article
- Structural similarity between defense peptide from wheat and scorpion neurotoxin permits rational functional design.The Journal of biological chemistry · 2014Article
- Interplay of physics and evolution in the likely origin of protein biochemical function.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- A Heritable Recombination system for synthetic Darwinian evolution in yeast.ACS synthetic biology · 2012Article
- Toward a systems biology perspective on enzyme evolution.The Journal of biological chemistry · 2012Review
- Computational approaches for rational design of proteins with novel functionalities.Computational and structural biotechnology journal · 2012Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzymes participating in different metabolic pathways often have similar catalytic mechanisms and structures, suggesting their evolution from a common ancestral precursor enzyme. We sought to create a precursor-like enzyme for N'-[(5'-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (ProFAR) isomerase (HisA; EC ) and phosphoribosylanthranilate (PRA) isomerase (TrpF; EC ), which catalyze similar reactions in the biosynthesis of the amino acids histidine and tryptophan and have a similar (betaalpha)(8)-barrel structure. Using random mutagenesis and selection, we generated several HisA variants that catalyze the TrpF reaction both in vivo and in vitro, and one of these variants retained significant HisA activity. A more detailed analysis revealed that a single amino acid exchange could establish TrpF activity on the HisA scaffold. These findings suggest that HisA and TrpF may have evolved from an ancestral enzyme of broader substrate specificity and underscore that (betaalpha)(8)-barrel enzymes are very suitable for the design of new catalytic activities.
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