ArticleProceedings of the National Academy of Sciences of the United States of America2011
Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 62 citations in OpenAlex.
- Experimental evolution reveals bifunctional genetic solutions to loss of trpF in Salmonella enterica.G3 (Bethesda, Md.) · 2026Article
- Functional shifts of the dual-substrate phosphoribosyl isomerase PriA from primary to specialized metabolism in rare Actinomycetota.Microbial genomics · 2026Article
- Conformational Dynamics and Catalytic Backups in a Hyper-thermostable Engineered Archaeal Protein Tyrosine Phosphatase.JACS Au · 2026Article
- Rescaling of Point Charges as a Way to Improve the Simple-to-Use Electrostatic Embedding Scheme Developed to Explore Enzyme Activity with QM-Oriented Software.Journal of chemical information and modeling · 2025Article
- Catalytic Redundancies and Conformational Plasticity Drives Selectivity and Promiscuity in Quorum Quenching Lactonases.JACS Au · 2024Article
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- Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase.Nature communications · 2023Article
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
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- The tryptophan biosynthetic pathway is essential for Mycobacterium tuberculosis to cause disease.Biochemical Society transactions · 2020Review
- How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation.The FEBS journal · 2020Review
- Mutational Pathways and Trade-Offs Between HisA and TrpF Functions: Implications for Evolution via Gene Duplication and Divergence.Frontiers in microbiology · 2020Article
- Identification and structural characterization of a histidinol phosphate phosphatase fromThe Journal of biological chemistry · 2018Article
- A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals.Frontiers in molecular biosciences · 2018Review
- Evolutionary convergence in the biosyntheses of the imidazole moieties of histidine and purines.PloS one · 2018Article
- Structural and functional innovations in the real-time evolution of new (βα)Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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- Harnessing Nature's Diversity: Discovering organophosphate bioscavenger characteristics among low molecular weight proteins.Scientific reports · 2016Article
- 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
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In histidine and tryptophan biosynthesis, two related isomerization reactions are generally catalyzed by two specific single-substrate enzymes (HisA and TrpF), sharing a similar (β/α)(8)-barrel scaffold. However, in some actinobacteria, one of the two encoding genes (trpF) is missing and the two reactions are instead catalyzed by one bisubstrate enzyme (PriA). To unravel the unknown mechanism of bisubstrate specificity, we used the Mycobacterium tuberculosis PriA enzyme as a model. Comparative structural analysis of the active site of the enzyme showed that PriA undergoes a reaction-specific and substrate-induced metamorphosis of the active site architecture, demonstrating its unique ability to essentially form two different substrate-specific actives sites. Furthermore, we found that one of the two catalytic residues in PriA, which are identical in both isomerization reactions, is recruited by a substrate-dependent mechanism into the active site to allow its involvement in catalysis. Comparison of the structural data from PriA with one of the two single-substrate enzymes (TrpF) revealed substantial differences in the active site architecture, suggesting independent evolution. To support these observations, we identified six small molecule compounds that inhibited both PriA-catalyzed isomerization reactions but had no effect on TrpF activity. Our data demonstrate an opportunity for organism-specific inhibition of enzymatic catalysis by taking advantage of the distinct ability for bisubstrate catalysis in the M. tuberculosis enzyme.
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