Ask about this productRelated genes to: PRODH2 antibody
- Gene:
- PRODH NIH gene
- Name:
- proline dehydrogenase 1
- Previous symbol:
- -
- Synonyms:
- HSPOX2, PRODH1, PIG6, PRODH2, TP53I6
- Chromosome:
- 22q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1996-12-12
- Date modifiied:
- 2016-10-05
- Gene:
- PRODH2 NIH gene
- Name:
- proline dehydrogenase 2
- Previous symbol:
- -
- Synonyms:
- HSPOX1
- Chromosome:
- 19q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-03
- Date modifiied:
- 2017-01-16
Related products to: PRODH2 antibody
Related articles to: PRODH2 antibody
- The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe. Here we investigated a close analog of NPPG, but-3-yn-2-ylglycine (B32G), distinguished by having a methyl group adjacent to the ethynyl group of the propargyl warhead. UV-visible spectroscopy shows that a bacterial PRODH catalyzes the oxidation of the S-enantiomer of B32G, a necessary first step in mechanism-based inactivation. In contrast, the enzyme does not react with the R-enantiomer. Enzyme activity assays show that S-B32G inhibits bacterial PRODH in a time-dependent manner consistent with covalent inactivation; however, the inactivation efficiency is ∼600-times lower than NPPG. We generated the crystal structure of PRODH inactivated by S-B32G at 1.68 Å resolution and found that inactivation induces a covalent link between the FAD N5 and the ε-nitrogen of an active site lysine, confirming that S-B32G follows the same mechanism as NPPG. Despite its lower inactivation efficiency at the purified bacterial enzyme, S-B32G exhibited comparable activity to NPPG against PRODH and PRODH2 in human cells and mouse livers. Molecular modeling is used to rationalize the stereospecificity of B32G. - Source: PubMed
Publication date: 2025/01/25
Meeks Kaylen RJi JuanScott Gary KCampbell Ashley CNix Jay CTadeo AdaEllerby Lisa MBenz Christopher CTanner John J - Epigenetic alterations are especially important in necrotizing enterocolitis (NEC). Here, we reported that histone deacetylase 8 (HDAC8) plays a previously unknown role in modulating arginine metabolism via acetylation of histone 3 lysine 9 (acetyl-H3K9) regulation during the pathogenesis of NEC. We found that HDAC8 was upregulated in humans and mice intestinal samples with NEC, while selective inhibition of HDAC8 expression ameliorated NEC. HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC) and arginine to ornithine (ARG1). The results showed that H3K9ac signal in the PRODH/PRODH2 promoter region was mediated by HDAC8. Additionally, the decreased concentration of butyric acid was strongly correlated with elevated HDAC8 levels and circulating arginine, which may result from an unbalanced Firmicutes/Bacteroidetes ratio. These results reveal previously underappreciated roles of microbial metabolites and HDAC8 to coordinate the arginine metabolism during NEC development. - Source: PubMed
Publication date: 2023/05/14
Guo TingHu ShaohuaXu WeijueZhou JinChen FengGao TingtingQu WenqianChen FalingLv ZhibaoLu Li - Proline is an amino acid that is degraded in the mitochondria by the sequential action of proline dehydrogenase (ProDH) and pyrroline-5-carboxylate dehydrogenase (P5CDH) to form glutamate. We investigated the phenotypes of Arabidopsis wild-type plants, the knockout prodh1 prodh2 double-mutant, and knockout p5cdh allelic mutants grown at low and high nitrate supplies. Surprisingly, only p5cdh presented lower seed yield and produced lighter seeds. Analyses of elements in above-ground organs revealed lower C concentrations in the p5cdh seeds. Determination of C, N, and dry matter partitioning among the above-ground organs revealed a major defect in stem-to-seed resource allocations in this mutant. Again surprisingly, defects in C, N, and biomass allocation to seeds dramatically increased in high-N conditions. 15N-labelling consistently confirmed the defect in N remobilization from the rosette and stem to seeds in p5cdh. Consequently, the p5cdh mutants produced morphologically abnormal, C-depleted seeds that displayed very low germination rates. The most striking result was the strong amplification of the N-remobilization defects in p5cdh under high nitrate supply, and interestingly this phenotype was not observed in the prodh1 prodh2 double-mutant irrespective of nitrate supply. This study reveals an essential role of P5CDH in carbon and nitrogen remobilization for reserve accumulation during seed development in Arabidopsis. - Source: PubMed
Dourmap CorentinMarmagne AnneLebreton SandrineClément GillesGuivarc'h AnneSavouré ArnouldMasclaux-Daubresse Céline - We previously reported that proline modulates root meristem size in by controlling the ratio between cell division and cell differentiation. Here, we show that proline metabolism affects the levels of superoxide anion (O) and hydrogen peroxide (HO), which, in turn, modulate root meristem size and root elongation. We found that hydrogen peroxide plays a major role in proline-mediated root elongation, and its effects largely overlap those induced by proline, influencing root meristem size, root elongation, and cell cycle. Though a combination of genetic and pharmacological evidence, we showed that the short-root phenotype of the proline-deficient , an mutant homozygous for and heterozygous for , is caused by HO accumulation and is fully rescued by an effective HO scavenger. Furthermore, by studying mutants devoid of ProDH activity, we disclosed the essential role of this enzyme in the modulation of root meristem size as the main enzyme responsible for HO production during proline degradation. Proline itself, on the contrary, may not be able to directly control the levels of HO, although it seems able to enhance the enzymatic activity of catalase (CAT) and ascorbate peroxidase (APX), the two most effective scavengers of HO in plant cells. We propose a model in which proline metabolism participates in a delicate antioxidant network to balance HO formation and degradation and fine-tune root meristem size in . - Source: PubMed
Publication date: 2022/06/05
Bauduin SaraLatini MartinaBelleggia IreneMigliore MartaBiancucci MarcoMattioli RobertoFrancioso AntonioMosca LucianaFunck DietmarTrovato Maurizio - Proline dehydrogenase (ProDH) is a flavoenzyme that catalyzes the oxidation of proline (Pro) into Δ1-pyrroline-5-carboxylate (P5C). In eukaryotes, ProDH coordinates with different Pro metabolism enzymes to control energy supply or stress responses signaling. Heterologous expression and crystallization of prokaryotic enzymes provided key data on their active center, folding capacity and oligomerization status. In contrast, eukaryotic ProDHs have not been crystallized so far, and their study as recombinant proteins remains limited. Plants contain two isoforms of ProDH with non-redundant functions. To contribute to the study of these enzymes, we describe the modeling, expression in E. coli, purification, and characterization of the Arabidopsis isoenzymes, AtProDH1 and AtProDH2. The 3D model suggested that both proteins adopt a distorted barrel structure (βα) with a cap formed by N-terminal α helices. The expression of two types of N-terminal deletion proteins indicated that this domain affected enzyme activity. Full-length enzymes had Km values similar to those of native proteins, whereas truncated proteins were inactive. Moreover, the first α helix proved to be necessary for AtProDH1 and AtProDH2 activities. Interestingly, both isoenzymes were able to oligomerize and this also required the first N-terminal α helix. Thus, we report the first insights into structure-function relationship of plant ProDHs demonstrating that the N-terminus, although not directly involved in catalysis, controls enzyme arrangement and activity. The resources generated here could be useful to analyze other plant ProDH features, such as its coordination with other enzymes, and differences between ProDH1 and ProDH2, providing new information on its effects on stress tolerance. - Source: PubMed
Publication date: 2020/06/13
Fabro GeorginaCislaghi Ana PaulaCondat FélixDeza Borau GermánAlvarez María Elena