ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structures of the PutA peripheral membrane flavoenzyme reveal a dynamic substrate-channeling tunnel and the quinone-binding site.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 70 citations in OpenAlex.
- Quinone-transporting filaments expand bioenergetic capacity in Gram-positive Bacillota.Nature microbiology · 2026Article
- Structural Principles of Covalent Flavin Modification in Oxidoreductases.Biochemistry · 2026Review
- Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.Archives of biochemistry and biophysics · 2025Article
- Noncovalent Inhibition and Covalent Inactivation of Proline Dehydrogenase by Analogs ofBiochemistry · 2024Article
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- Proline Dehydrogenase and Pyrroline 5 Carboxylate Dehydrogenase fromPathogens (Basel, Switzerland) · 2023Article
- Structure-based engineering of minimal proline dehydrogenase domains for inhibitor discovery.Protein engineering, design & selection : PEDS · 2022Article
- Structure-affinity relationships of reversible proline analog inhibitors targeting proline dehydrogenase.Organic & biomolecular chemistry · 2022Article
- N-Propargylglycine: a unique suicide inhibitor of proline dehydrogenase with anticancer activity and brain-enhancing mitohormesis properties.Amino acids · 2021Article
- Photoinduced Covalent Irreversible Inactivation of Proline Dehydrogenase by S-Heterocycles.ACS chemical biology · 2021Article
- Probing the function of a ligand-modulated dynamic tunnel in bifunctional proline utilization A (PutA).Archives of biochemistry and biophysics · 2021Article
- Structural analysis of prolines and hydroxyprolines binding to the l-glutamate-γ-semialdehyde dehydrogenase active site of bifunctional proline utilization A.Archives of biochemistry and biophysics · 2021Article
- Co-localization and confinement of ecto-nucleotidases modulate extracellular adenosine nucleotide distributions.PLoS computational biology · 2020Article
- Covalent Modification of the Flavin in Proline Dehydrogenase by Thiazolidine-2-Carboxylate.ACS chemical biology · 2020Article
- Appropriate Activity Assays Are Crucial for the Specific Determination of Proline Dehydrogenase and Pyrroline-5-Carboxylate Reductase Activities.Frontiers in plant science · 2020Article
- Gene Expression ofInternational journal of molecular sciences · 2019Article
- Domain cross-talk within a bifunctional enzyme provides catalytic and allosteric functionality in the biosynthesis of aromatic amino acids.The Journal of biological chemistry · 2019Article
- Structural and Biochemical Characterization of Aldehyde Dehydrogenase 12, the Last Enzyme of Proline Catabolism in Plants.Journal of molecular biology · 2019Article
- Structural Biology of Proline Catabolic Enzymes.Antioxidants & redox signaling · 2019Review
- Role of Proline in Pathogen and Host Interactions.Antioxidants & redox signaling · 2019Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Proline utilization A (PutA) proteins are bifunctional peripheral membrane flavoenzymes that catalyze the oxidation of L-proline to L-glutamate by the sequential activities of proline dehydrogenase and aldehyde dehydrogenase domains. Located at the inner membrane of Gram-negative bacteria, PutAs play a major role in energy metabolism by coupling the oxidation of proline imported from the environment to the reduction of membrane-associated quinones. Here, we report seven crystal structures of the 1,004-residue PutA from Geobacter sulfurreducens, along with determination of the protein oligomeric state by small-angle X-ray scattering and kinetic characterization of substrate channeling and quinone reduction. The structures reveal an elaborate and dynamic tunnel system featuring a 75-Å-long tunnel that links the two active sites and six smaller tunnels that connect the main tunnel to the bulk medium. The locations of these tunnels and their responses to ligand binding and flavin reduction suggest hypotheses about how proline, water, and quinones enter the tunnel system and where L-glutamate exits. Kinetic measurements show that glutamate production from proline occurs without a lag phase, consistent with substrate channeling and implying that the observed tunnel is functionally relevant. Furthermore, the structure of reduced PutA complexed with menadione bisulfite reveals the elusive quinone-binding site. The benzoquinone binds within 4.0 Å of the flavin si face, consistent with direct electron transfer. The location of the quinone site implies that the concave surface of the PutA dimer approaches the membrane. Altogether, these results provide insight into how PutAs couple proline oxidation to quinone reduction.
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