ArticleProceedings of the National Academy of Sciences of the United States of America2017
Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed.
- Whole genome insights into hydrocarbon degradation and antimicrobial resistance in Staphylococcus epidermidis CSR1 isolated from oil-contaminated soil.Archives of microbiology · 2026Article
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- Cloning, purification and possible use of a Bacillus nitroreductase in biotechnological applications.Scientific reports · 2026Article
- Novel TdsD nitroreductase: characterization of kinetics and substrate specificity.Biotechnology letters · 2025Article
- Article
- Exploring Large Protein Sequence Space through Homology- and Representation-based Hierarchical Clustering.Molecular biology and evolution · 2025Article
- Mining versatile feruloyl esterases: phylogenetic classification, structural features, and deep learning model.Bioresources and bioprocessing · 2025Article
- Polar Interactions between Substrate and Flavin Control Iodotyrosine Deiodinase Function.Biochemistry · 2024Article
- Article
- Structural Evaluation of a Nitroreductase Engineered for Improved Activation of the 5-Nitroimidazole PET Probe SN33623.International journal of molecular sciences · 2024Article
- Misregulation of bromotyrosine compromises fertility in maleProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Substrate Specificities of Variants of Barley (1,3)- and (1,3;1,4)-β-d-Glucanases Resulting from Mutagenesis and Segment Hybridization.Biochemistry · 2024Article
- Cyclodipeptide oxidase is an enzyme filament.Nature communications · 2024Article
- The Catalysis Mechanism ofInternational journal of molecular sciences · 2024Article
- Remote loop evolution reveals a complex biological function for chitinase enzymes beyond the active site.Nature communications · 2024Article
- A metagenomic library cloning strategy that promotes high-level expression of captured genes to enable efficient functional screening.Cell chemical biology · 2023Article
- Enzyme function and evolution through the lens of bioinformatics.The Biochemical journal · 2023Review
- Tailored photoenzymatic systems for selective reduction of aliphatic and aromatic nitro compounds fueled by light.Nature communications · 2023Article
- The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase.RSC chemical biology · 2023Article
- An objective criterion to evaluate sequence-similarity networks helps in dividing the protein family sequence space.PLoS computational biology · 2023Article
11 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination of tools that include large-scale phylogenetic reconstruction to determine the sequence, structural, and functional relationships of the functionally diverse flavin mononucleotide-dependent nitroreductase (NTR) superfamily (>24,000 sequences from all domains of life, 54 structures, and >10 enzymatic functions). Our results suggest an evolutionary model in which contemporary subgroups of the superfamily have diverged in a radial manner from a minimal flavin-binding scaffold. We identified the structural design principle for this divergence: Insertions at key positions in the minimal scaffold that, combined with the fixation of key residues, have led to functional specialization. These results will aid future efforts to delineate the emergence of functional diversity in enzyme superfamilies, provide clues for functional inference for superfamily members of unknown function, and facilitate rational redesign of the NTR scaffold.
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