ArticleNature structural & molecular biology2020
Ancestral-sequence reconstruction unveils the structural basis of function in mammalian FMOs.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 95 citations in OpenAlex.
- A programmable bifunctional flavoenzyme for direct amine-to-ester conversion.Science advances · 2026Article
- Ancestral Sequence Reconstruction of the Ethylene-Forming Enzyme.Biochemistry · 2025Article
- Article
- Ancestral sequence reconstruction as a tool for structural analysis of modular polyketide synthases.Nature communications · 2025Article
- Ancestral evolution of oxidase activity in a class of (S)-nicotine and (S)-6-hydroxynicotine-degrading flavoenzymes.The Journal of biological chemistry · 2025Article
- SsDiHal: discovery and engineering of a novel tryptophan dihalogenase.Journal of biological engineering · 2025Article
- Design of ancestral mammalian alkaline phosphatase bearing high stability and productivity.Applied and environmental microbiology · 2024Article
- Transcriptional analysis of C. elegans fmos at different life stages and their roles in ageing.Molecular genetics and genomics : MGG · 2024Article
- Exploring Trimethylaminuria: Genetics and Molecular Mechanisms, Epidemiology, and Emerging Therapeutic Strategies.Biology · 2024Review
- Ancestral Sequence Reconstruction to Enable Biocatalytic Synthesis of Azaphilones.Journal of the American Chemical Society · 2024Article
- Characterization of the Flavin-Dependent Monooxygenase Involved in the Biosynthesis of the Nocardiosis-Associated Polyketide†.Biochemistry · 2024Article
- Bioinformatics Goes Viral: I. Databases, Phylogenetics and Phylodynamics Tools for Boosting Virus Research.Viruses · 2024Review
- Multiple Functions of Compatible Solute Ectoine and Strategies for Constructing Overproducers for Biobased Production.Molecular biotechnology · 2024Review
- In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis.Nature catalysis · 2024Article
- Guiding discovery of protein sequence-structure-function modeling.Bioinformatics (Oxford, England) · 2024Article
- Structural basis of regioselective tryptophan dibromination by the single-component flavin-dependent halogenase AetF.Acta crystallographica. Section D, Structural biology · 2023Article
- Deciphering the evolution of flavin-dependent monooxygenase stereoselectivity using ancestral sequence reconstruction.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Cold-Active Flavin-Dependent Monooxygenase fromACS catalysis · 2023Article
- Evolution of enzyme functionality in the flavin-containing monooxygenases.Nature communications · 2023Article
- Genomic Survey of Flavin Monooxygenases in Wild and Cultivated Rice Provides Insight into Evolution and Functional Diversities.International journal of molecular sciences · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flavin-containing monooxygenases (FMOs) are ubiquitous in all domains of life and metabolize a myriad of xenobiotics, including toxins, pesticides and drugs. However, despite their pharmacological importance, structural information remains bereft. To further our understanding behind their biochemistry and diversity, we used ancestral-sequence reconstruction, kinetic and crystallographic techniques to scrutinize three ancient mammalian FMOs: AncFMO2, AncFMO3-6 and AncFMO5. Remarkably, all AncFMOs could be crystallized and were structurally resolved between 2.7- and 3.2-Å resolution. These crystal structures depict the unprecedented topology of mammalian FMOs. Each employs extensive membrane-binding features and intricate substrate-profiling tunnel networks through a conspicuous membrane-adhering insertion. Furthermore, a glutamate-histidine switch is speculated to induce the distinctive Baeyer-Villiger oxidation activity of FMO5. The AncFMOs exhibited catalysis akin to human FMOs and, with sequence identities between 82% and 92%, represent excellent models. Our study demonstrates the power of ancestral-sequence reconstruction as a strategy for the crystallization of proteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.