ArticleThe Journal of biological chemistry2014
Evidence for hysteretic substrate channeling in the proline dehydrogenase and Δ1-pyrroline-5-carboxylate dehydrogenase coupled reaction of proline utilization A (PutA).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Time-Dependent Kinetic Complexities in Enzyme Assays: A Review.Biomolecules · 2025Review
- The Proline Dehydrogenase GeneInternational journal of molecular sciences · 2025Article
- Proline Dehydrogenase and Pyrroline 5 Carboxylate Dehydrogenase fromPathogens (Basel, Switzerland) · 2023Article
- Modular reconstruction and optimization of the trans-4-hydroxy-L-proline synthesis pathway in Escherichia coli.Microbial cell factories · 2022Article
- Article
- 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
- Covalent Modification of the Flavin in Proline Dehydrogenase by Thiazolidine-2-Carboxylate.ACS chemical biology · 2020Article
- Structural Biology of Proline Catabolic Enzymes.Antioxidants & redox signaling · 2019Review
- Role of Proline in Pathogen and Host Interactions.Antioxidants & redox signaling · 2019Review
- Functional Impact of the N-terminal Arm of Proline Dehydrogenase from Thermus thermophilus.Molecules (Basel, Switzerland) · 2018Article
- Structural Basis for the Substrate Inhibition of Proline Utilization A by Proline.Molecules (Basel, Switzerland) · 2017Article
- Article
- Structure, function, and mechanism of proline utilization A (PutA).Archives of biochemistry and biophysics · 2017Review
- Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure.The FEBS journal · 2017Article
- Identification of a Conserved Histidine As Being Critical for the Catalytic Mechanism and Functional Switching of the Multifunctional Proline Utilization A Protein.Biochemistry · 2017Article
- Structure and characterization of a class 3B proline utilization A: Ligand-induced dimerization and importance of the C-terminal domain for catalysis.The Journal of biological chemistry · 2017Article
- Resolving the cofactor-binding site in the proline biosynthetic enzyme human pyrroline-5-carboxylate reductase 1.The Journal of biological chemistry · 2017Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
PutA (proline utilization A) is a large bifunctional flavoenzyme with proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH) domains that catalyze the oxidation of l-proline to l-glutamate in two successive reactions. In the PRODH active site, proline undergoes a two-electron oxidation to Δ(1)-pyrroline-5-carboxlylate, and the FAD cofactor is reduced. In the P5CDH active site, l-glutamate-γ-semialdehyde (the hydrolyzed form of Δ(1)-pyrroline-5-carboxylate) undergoes a two-electron oxidation in which a hydride is transferred to NAD(+)-producing NADH and glutamate. Here we report the first kinetic model for the overall PRODH-P5CDH reaction of a PutA enzyme. Global analysis of steady-state and transient kinetic data for the PRODH, P5CDH, and coupled PRODH-P5CDH reactions was used to test various models describing the conversion of proline to glutamate by Escherichia coli PutA. The coupled PRODH-P5CDH activity of PutA is best described by a mechanism in which the intermediate is not released into the bulk medium, i.e., substrate channeling. Unexpectedly, single-turnover kinetic experiments of the coupled PRODH-P5CDH reaction revealed that the rate of NADH formation is 20-fold slower than the steady-state turnover number for the overall reaction, implying that catalytic cycling speeds up throughput. We show that the limiting rate constant observed for NADH formation in the first turnover increases by almost 40-fold after multiple turnovers, achieving half of the steady-state value after 15 turnovers. These results suggest that EcPutA achieves an activated channeling state during the approach to steady state and is thus a new example of a hysteretic enzyme. Potential underlying causes of activation of channeling are discussed.
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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.