Crystal Structure of Human Pyrroline-5-carboxylate Reductase

Meng, Zhen; Lou, Zhiyong; Liu, Zhe; Li, Ming; Zhao, Xiaodong; Bartlam, Mark; Rao, Zihe

doi:10.1016/j.jmb.2006.04.053

Cited by 60 publications

(105 citation statements)

References 35 publications

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Section: P5c Reductasementioning

confidence: 99%

“…P5CR is conserved among bacteria, plants, insects, and vertebrates (82,103). X-ray crystal structures of P5CR from different organisms, including humans, have been solved showing a conserved N-terminal Rossmann fold for NADPH binding (6,82). In plants, P5CR is not only located in the cytosol but has also been shown to be expressed in chloroplasts (123,131).…”

Section: P5c Reductasementioning

confidence: 99%

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Proline Mechanisms of Stress Survival

Liang

Zhang

Natarajan

et al. 2013

Antioxidants & Redox Signaling

888

576

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Significance: The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress adaptor molecule indicates that proline has a fundamental biological role in stress response. Understanding the mechanisms by which proline enhances abiotic/biotic stress response will facilitate agricultural crop research and improve human health. Recent Advances: It is now recognized that proline metabolism propels cellular signaling processes that promote cellular apoptosis or survival. Studies have shown that proline metabolism influences signaling pathways by increasing reactive oxygen species (ROS) formation in the mitochondria via the electron transport chain. Enhanced ROS production due to proline metabolism has been implicated in the hypersensitive response in plants, lifespan extension in worms, and apoptosis, tumor suppression, and cell survival in animals. Critical Issues: The ability of proline to influence disparate cellular outcomes may be governed by ROS levels generated in the mitochondria. Defining the threshold at which proline metabolic enzyme expression switches from inducing survival pathways to cellular apoptosis would provide molecular insights into cellular redox regulation by proline. Are ROS the only mediators of proline metabolic signaling or are other factors involved? Future Directions: New evidence suggests that proline biosynthesis enzymes interact with redox proteins such as thioredoxin. An important future pursuit will be to identify other interacting partners of proline metabolic enzymes to uncover novel regulatory and signaling networks of cellular stress response. Antioxid. Redox Signal. 19, 998-1011.

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Section: P5c Reductasementioning

confidence: 99%

Section: P5c Reductasementioning

confidence: 99%

Proline Mechanisms of Stress Survival

Liang

Zhang

Natarajan

et al. 2013

Antioxidants & Redox Signaling

888

576

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“…First, Pycr1 is a mitochondrial enzyme that catalyzes the final step in the conversion of pyrroline-5-carboxylate (P5C) to proline (Lorans and Phang, 1981); therefore, the observed decreases in Pycr1 and proline likely indicates decreased proline biosynthesis. Notably, the Pycr1-dependent P5C/proline cycle has a dramatic effect on cellular energetic and physiological processes, such as mitochondrial electron transport ( Meng et al, 2006). Second, caytaxin is a brain-specific protein with relatively higher cerebellar and hippocampal expression (Buschdorf et al, 2006) that inhibits glutaminase, an enzyme that converts glutamine to glutamate.…”

Section: Perturbation Of Amino Acid Metabolismmentioning

confidence: 99%

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum

Shao

Chen

Fan

et al. 2015

OMICS: A Journal of Integrative Biology

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Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel ''-omics'' insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD.

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“…The crystal structure of human P5CR1 have been reported recently [13,14]. The 2.8 Angstroms (Å) resolution structure of the P5CR1 apo enzyme and its 3.1 Å resolution ternary complex with NAD(P)H and substrate-analog demonstrated that human P5CR1 possesses a decameric architecture with five homodimer subunits.…”

Section: Human P5cr1 Protein Structure and Associated Diseasesmentioning

confidence: 96%

“…A recent study by Krishnan and colleagues [12] showed over expression of P5CR1 resulted in 2-fold higher proline content, significantly lowered free radical levels, and increased cell survival. Another studies showed that increased P5CR1 activity was measurable in pulmonary and colorectal tumors [13,14]. In contrast, mammalian P5CR2 and P5CRL are relatively new and not well studied.…”

Section: Introductionmentioning

confidence: 99%

Mammalian P5CR and P5CDH: Protein Structure and Disease Association

Hu¹

2014

SOJB

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Crystal Structure of Human Pyrroline-5-carboxylate Reductase

Cited by 60 publications

References 35 publications

Proline Mechanisms of Stress Survival

Proline Mechanisms of Stress Survival

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum

Mammalian P5CR and P5CDH: Protein Structure and Disease Association

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