The bisphosphonomethyl analogue of 2,3-bisphosphoglycerate inhibits yeast but not wheat-germ phosphoglycerate mutase.
Ontology highlight
ABSTRACT:
SUBMITTER: McAleese SM
PROVIDER: S-EPMC1147850 | biostudies-other | 1987 Apr
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Burkholderia pseudomallei is a soil-dwelling bacterium endemic to Southeast Asia and Northern Australia. Burkholderia is responsible for melioidosis, a serious infection of the skin. The enzyme 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (PGAM) catalyzes the interconversion of 3-phosphoglycerate and 2-phosphoglycerate, a key step in the glycolytic pathway. As such it is an extensively studied enzyme and X-ray crystal structures of PGAM enzymes from multiple species have been elucidated. Vanadate is a phosphate mimic that is a powerful tool for studying enzymatic mechanisms in phosphoryl-transfer enzymes such as phosphoglycerate mutase. However, to date no X-ray crystal structures of phosphoglycerate mutase have been solved with vanadate acting as a substrate mimic. Here, two vanadate complexes together with an ensemble of substrate and fragment-bound structures that provide a comprehensive picture of the function of the Burkholderia enzyme are reported.
| S-EPMC3169400 | biostudies-literature
Project description:Lower glycolysis involves a series of reversible reactions, which interconvert intermediates that also feed anabolic pathways. 3-phosphoglycerate (3-PG) is an abundant lower glycolytic intermediate that feeds serine biosynthesis via the enzyme phosphoglycerate dehydrogenase, which is genomically amplified in several cancers. Phosphoglycerate mutase 1 (PGAM1) catalyzes the isomerization of 3-PG into the downstream glycolytic intermediate 2-phosphoglycerate (2-PG). PGAM1 needs to be histidine phosphorylated to become catalytically active. We show that the primary PGAM1 histidine phosphate donor is 2,3-bisphosphoglycerate (2,3-BPG), which is made from the glycolytic intermediate 1,3-bisphosphoglycerate (1,3-BPG) by bisphosphoglycerate mutase (BPGM). When BPGM is knocked out, 1,3-BPG can directly phosphorylate PGAM1. In this case, PGAM1 phosphorylation and activity are decreased, but nevertheless sufficient to maintain normal glycolytic flux and cellular growth rate. 3-PG, however, accumulates, leading to increased serine synthesis. Thus, one biological function of BPGM is controlling glycolytic intermediate levels and thereby serine biosynthetic flux.
| S-EPMC5605442 | biostudies-literature
Project description:The enzyme 2,3 bisphosphoglycerate mutase (BPGM) catalyzes the production of 2,3-bisphosphoglycerate (2,3-BPG). The main role of 2,3-BPG is to shift the equilibrium of hemoglobin toward the deoxy-state, accounting for the notion that 2,3-BPG production would appear to be solely useful in cells which contain hemoglobin. 2,3-BPG level determines the baseline O2-Hb affinity at rest, which shows a broad diversity among human population. The kidney is the site of oxygen sensing and erythropoietin synthesis through the action of the hypoxia-inducible factor (HIF) transcription factors, especially HIF-2. We observed a marked BPGM expression in distal parts of renal tubules that is elevated during kidney injury, thus, indicating cellular functions of BPGM not related to oxygen binding to hemoglobin. We, thus, explored the function of renal BPGM, particularly as related to down-stream metabolic effects.
2025-05-06 | PXD033095 | Pride
Project description:The enzyme 2,3 bisphosphoglycerate mutase (BPGM) catalyzes the production of 2,3-bisphosphoglycerate (2,3-BPG). The main role of 2,3-BPG is to shift the equilibrium of hemoglobin toward the deoxy-state, accounting for the notion that 2,3-BPG production would appear to be solely useful in cells which contain hemoglobin. 2,3-BPG level determines the baseline O2-Hb affinity at rest, which shows a broad diversity among human population. The kidney is the site of oxygen sensing and erythropoietin synthesis through the action of the hypoxia-inducible factor (HIF) transcription factors, especially HIF-2. We observed a marked BPGM expression in distal parts of renal tubules that is elevated during kidney injury, thus, indicating cellular functions of BPGM not related to oxygen binding to hemoglobin. We, thus, explored the function of renal BPGM, particularly as related to down-stream metabolic effects.
2025-05-06 | PXD040789 | Pride
Project description:Aim2,3-bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney.MethodsA tubular-specific, doxycycline-inducible Bpgm-knockout mouse model was generated. Histological, immunofluorescence, and proteomic analyses were conducted to examine the localization of BPGM expression and the impact of its knockout on kidney structure and function. In vitro studies were performed to investigate the metabolic consequences of Bpgm knockdown under osmotic stress.ResultsBPGM expression was localized to the distal nephron and was absent in proximal tubules. Inducible knockout of Bpgm resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed involvement of BPGM in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation. In vitro, Bpgm knockdown led to enhanced glycolysis, decreased reactive oxygen species elimination capacity under osmotic stress, and increased apoptosis. Furthermore, interactions between nephron segments and immune cells in the kidney suggested a mechanism for propagating stress signals from distal to proximal tubules.ConclusionBPGM fulfills critical functions beyond the erythrocyte in maintaining glucose metabolism in the distal nephron. Its absence leads to metabolic imbalances, increased oxidative stress, inflammation, and ultimately kidney injury.
| S-EPMC11674375 | biostudies-literature
Project description:Acidovorax citrulli (Ac) is a gram-negative bacterium that causes bacterial fruit blotch (BFB) disease in cucurbit crops including watermelon. However, despite the great economic losses caused by this disease worldwide, Ac-resistant watermelon cultivars have not been developed. Therefore, characterizing the virulence factors/mechanisms of Ac would enable the development of effective control strategies against BFB disease. The 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (BdpM) is known to participate in the glycolysis and gluconeogenesis pathways. However, the roles of the protein have not been characterized in Ac. To elucidate the functions of BdpmAc (Bdpm in Ac), comparative proteomic analysis and diverse phenotypic assays were conducted using a bdpmAc knockout mutant (bdpmAc:Tn) and a wild-type strain. The virulence of the mutant to watermelon was remarkably reduced in both germinated seed inoculation and leaf infiltration assays. Moreover, the mutant could not grow with fructose or pyruvate as a sole carbon source. However, the growth of the mutant was restored to levels similar to those of the wild-type strain in the presence of both fructose and pyruvate. Comparative proteomic analyses revealed that diverse proteins involved in motility and wall/membrane/envelop biogenesis were differentially abundant. Furthermore, the mutant exhibited decreased biofilm formation and twitching halo size. Interestingly, the mutant exhibited a higher tolerance against osmotic stress. Overall, our findings suggest that BdpmAc affects the virulence, glycolysis/gluconeogenesis, biofilm formation, twitching halo size, and osmotic tolerance of Ac, suggesting that this protein has pleiotropic properties. Collectively, our findings provide fundamental insights into the functions of a previously uncharacterized phosphoglycerate mutase in Ac.
| S-EPMC9681784 | biostudies-literature
Project description:1. The properties and kinetics of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutases are discussed. There are at least three possible mechanisms for the reaction: (i) a phosphoenzyme (Ping Pong) mechanism; (ii) an intermolecular transfer of phosphate from 2,3-diphosphoglycerate to the substrates (sequential mechanism); (iii) an intramolecular transfer of phosphate. It is concluded that these mechanisms cannot be distinguished by conventional kinetic measurements. 2. The fluxes for the different mechanisms are calculated and it is shown that it should be possible to distinguish between the mechanisms by appropriate induced-transport tests and by comparing the fluxes of (32)P- and (14)C-labelled substrates at chemical equilibrium. 3. With (14)C-labelled substrates no induced transport was found over a wide concentration range, and with (32)P-labelled substrates co-transport occurred that was independent of concentration over a twofold range. (14)C-labelled substrates exchange at twice the rate of (32)P-labelled substrates at chemical equilibrium. The results were completely in accord with a phosphoenzyme mechanism and indicated a rate constant for the isomerization of the phosphoenzyme of not less than 4x10(6)s(-1). The intramolecular transfer of phosphate (and intermolecular transfer between two or more molecules of substrate) were completely excluded. The intermolecular transfer of phosphate from 2,3-diphosphoglycerate would have been compatible with the results only if the K(m) for 2-phosphoglycerate had been over 7.5-fold smaller than the observed value and if an isomerization of the enzyme-2,3-diphosphoglycerate complex had been the major rate-limiting step in the reaction. 4. The very rapid isomerization of the phosphoenzyme that the experiments demonstrate suggests a mechanism that does not involve a formal isomerization. According to this new scheme the enzyme is closely related mechanistically and perhaps evolutionarily to a 2,3-diphosphoglycerate diphosphatase.
| S-EPMC1174419 | biostudies-other
Project description:To investigate the importance of functional regulation of PGAM2 by SUMO conjugation in the context of myogenic differentiation. We performed RNAseq analysis of WT and sumoylation deficient mutant (K176R mutatant) C2C12 cells at different differentiation days, i.e. day 0 and day4, respectively (n=3/group).
2023-01-11 | GSE220249 | GEO
Project description:PurposeOxygen is vital for oocyte maturation; however, oxygen regulation within ovarian follicles is not fully understood. Hemoglobin is abundant within the in vivo matured oocyte, indicating potential function as an oxygen regulator. However, hemoglobin is significantly reduced following in vitro maturation (IVM). The molecule 2,3-bisphosphoglycerate (2,3-BPG) is essential in red blood cells, facilitating release of oxygen from hemoglobin. Towards understanding the role of 2,3-BPG in the oocyte, we characterized gene expression and protein abundance of bisphosphoglycerate mutase (Bpgm), which synthesizes 2,3-BPG, and whether this is altered under low oxygen or hemoglobin addition during IVM.MethodsHemoglobin and Bpgm expression within in vivo matured human cumulus cells and mouse cumulus-oocyte complexes (COCs) were evaluated to determine physiological levels of Bpgm. During IVM, Bpgm gene expression and protein abundance were analyzed in the presence or absence of low oxygen (2% and 5% oxygen) or exogenous hemoglobin.ResultsThe expression of Bpgm was significantly lower than hemoglobin when mouse COCs were matured in vivo. Following IVM at 20% oxygen, Bpgm gene expression and protein abundance were significantly higher compared to in vivo. At 2% oxygen, Bpgm was significantly higher compared to 20% oxygen, while exogenous hemoglobin resulted in significantly lower Bpgm in the COC.ConclusionHemoglobin and 2,3-BPG may play a role within the maturing COC. This study shows that IVM increases Bpgm within COCs compared to in vivo. Decreasing oxygen concentration and the addition of hemoglobin altered Bpgm, albeit not to levels observed in vivo.
| S-EPMC8266955 | biostudies-literature
Project description:It has been reported [Smith, McWilliams & Hass (1986) Biochem. Biophys. Res. Commun. 136, 336-340] that addition of certain metal ions, notably Co2+ and Mn2+, promoted the refolding of denatured phosphoglycerate mutase from wheat germ. We have re-investigated these experiments and have shown that, when precautions are taken to avoid artefacts in the assay system, the metal ions do not promote any re-activation of the denatured wheat-germ or Aspergillus nidulans enzymes. An alternative explanation is offered for the observations of Smith et al. (1986).
| S-EPMC1149113 | biostudies-other