ReviewAntioxidants & redox signaling2019
Structural Biology of Proline Catabolic Enzymes.
Review in Antioxidants & redox signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Structural Principles of Covalent Flavin Modification in Oxidoreductases.Biochemistry · 2026Review
- Measurement of δMetabolites · 2025Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression.Nature cell biology · 2025Article
- Crystallographic Fragment Screening of a Bifunctional Proline Catabolic Enzyme Reveals New Inhibitor Templates for Proline Dehydrogenase and L-Glutamate-γ-semialdehyde Dehydrogenase.Molecules (Basel, Switzerland) · 2024Article
- Proline catabolism is a key factor facilitating Candida albicans pathogenicity.PLoS pathogens · 2023Article
- Conformational Preferences of Pyridone Adenine Dinucleotides from Molecular Dynamics Simulations.International journal of molecular sciences · 2022Article
- Transcriptomic Analysis Reveals the Role of tmRNA on Biofilm Formation inMicroorganisms · 2022Article
- Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention.International journal of molecular sciences · 2022Review
- 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
- Amino Acid Sensing and Assimilation by the Fungal PathogenPathogens (Basel, Switzerland) · 2021Review
- N-Propargylglycine: a unique suicide inhibitor of proline dehydrogenase with anticancer activity and brain-enhancing mitohormesis properties.Amino acids · 2021Article
- Perspectives, past, present and future: the proline cycle/proline-collagen regulatory axis.Amino acids · 2021Article
- Evidence for Proline Catabolic Enzymes in the Metabolism of Thiazolidine Carboxylates.Biochemistry · 2021Article
- Probing the function of a ligand-modulated dynamic tunnel in bifunctional proline utilization A (PutA).Archives of biochemistry and biophysics · 2021Article
- P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis.International journal of molecular sciences · 2021Review
- Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans-4-hydroxy-L-proline.Protein science : a publication of the Protein Society · 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
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
significanceProline catabolism refers to the 4-electron oxidation of proline to glutamate catalyzed by the enzymes proline dehydrogenase (PRODH) and l-glutamate γ-semialdehyde dehydrogenase (GSALDH, or ALDH4A1). These enzymes and the intermediate metabolites of the pathway have been implicated in tumor growth and suppression, metastasis, hyperprolinemia metabolic disorders, schizophrenia susceptibility, life span extension, and pathogen virulence and survival. In some bacteria, PRODH and GSALDH are combined into a bifunctional enzyme known as proline utilization A (PutA). PutAs are not only virulence factors in some pathogenic bacteria but also fascinating systems for studying the coordination of metabolic enzymes via substrate channeling. Recent Advances: The past decade has seen an explosion of structural data for proline catabolic enzymes. This review surveys these structures, emphasizing protein folds, substrate recognition, oligomerization, kinetic mechanisms, and substrate channeling in PutA. CRITICAL ISSUES: Major unsolved structural targets include eukaryotic PRODH, the complex between monofunctional PRODH and monofunctional GSALDH, and the largest of all PutAs, trifunctional PutA. The structural basis of PutA-membrane association is poorly understood. Fundamental aspects of substrate channeling in PutA remain unknown, such as the identity of the channeled intermediate, how the tunnel system is activated, and the roles of ancillary tunnels. FUTURE DIRECTIONS: New approaches are needed to study the molecular and in vivo mechanisms of substrate channeling. With the discovery of the proline cycle driving tumor growth and metastasis, the development of inhibitors of proline metabolic enzymes has emerged as an exciting new direction. Structural biology will be important in these endeavors.
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Registered trials
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.