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PloS One 2023It has been proposed that the composition of the culture medium, especially its amino acids, is an important part of getting microspore androgenesis to occur in some...
It has been proposed that the composition of the culture medium, especially its amino acids, is an important part of getting microspore androgenesis to occur in some plants. However, there have been far fewer studies done on the Solanaceae family. In this study, we studied what happened to eggplant microspore culture when we mixed casein hydrolysate (0 and 100 mg L-1) with four amino acids: proline (0, 100, 500, and 900 mg L-1), glutamine (0 and 800 mg L-1), serine (0 and 100 mg L-1), and alanine (0 and 100 mg L-1). The results showed that a combination of 800 mg L-1 of glutamine, 100 mg L-1 of serine, 100 mg L-1 of casein hydrolysate, and 500 mg L-1 of proline produced the maximum number of calli per Petri dish (938). Calli had a globular shape and a compact appearance when formed in media containing 500 mg L-1 of proline (alone or combined with serine, alanine, and/or casein hydrolysate). Most of these structures were observed in a medium with 500 mg L-1 of proline, 100 mg L-1 of casein hydrolysate, and 100 mg L-1 of serine. We also investigated what happened when gum arabic (2400, 2600, 3600, 4600, and 5600 mg L-1) was combined with proline (0 and 500 mg L-1), casein hydrolysate (0 and 100 mg L-1), and glutamine (0, 400, and 800 mg L-1). The findings demonstrated the involvement of proline in the increase of calli. Overall, the results give us new information about how amino acids work in eggplant microspore culture and suggest that proline can move this plant's microspore androgenesis pathway forward.
Topics: Amino Acids; Solanum melongena; Glutamine; Proline; Alanine; Serine
PubMed: 37289731
DOI: 10.1371/journal.pone.0286809 -
Journal of Microbiology, Immunology,... Apr 2021K. pneumoniae, a common pathogen that frequently causes bacteremia in clinic, is unresponsive to most of known antibiotics, thus cumulatively exacerbating empirical...
OBJECTIVE
K. pneumoniae, a common pathogen that frequently causes bacteremia in clinic, is unresponsive to most of known antibiotics, thus cumulatively exacerbating empirical therapy failures. Effective strategies to control Klebsiella pneumoniae bacteremia are in high demand. One possibility is to mobilize host defense mechanisms against bacterial pathogens.
METHODS
We employed GC/MS-based metabolomics to identify the changes of metabolism in mice challenged by K. pneumoniae (ATCC 43816) bacteremia.
RESULTS
Compared with the mice that compromised from K. pneumoniae bacteremia, mice that survived from infection displayed the varied metabolomic profile. The differential analysis of metabolome showed that Ethanedioic acid, d-Glucose, l-Glutamine, Myo-inositol, and l-Proline were more likely associated with the host surviving a K. pneumoniae bacteremia. Further pathway enrichment analysis proposed that arginine and proline metabolism involved in outcome of K. pneumoniae bacteremia. The follow-up data showed that exogenous l-Proline but not d-Proline could decline the loads of Klebsiella pneumonia in infected blood and tissues (lung, liver and spleen) and increase the mouse survival.
CONCLUSION
Our study provides an exercisable strategy of identifying metabolic biomarkers from surviving host and highlights the possibility of utilizing the metabolic biomarker as a therapy for K. pneumoniae bacteremia.
Topics: Animals; Anti-Bacterial Agents; Arginine; Bacteremia; Biomarkers; Disease Models, Animal; Female; Klebsiella Infections; Klebsiella pneumoniae; Metabolomics; Mice; Mice, Inbred C57BL; Proline
PubMed: 31324551
DOI: 10.1016/j.jmii.2019.05.013 -
EMBO Molecular Medicine Jul 2023Prolyl-tRNA synthetase 1 (PARS1) has attracted much interest in controlling pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases....
Prolyl-tRNA synthetase 1 (PARS1) has attracted much interest in controlling pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases. However, there are concerns about its catalytic inhibition for potential adverse effects on global protein synthesis. We developed a novel compound, DWN12088, whose safety was validated by clinical phase 1 studies, and therapeutic efficacy was shown in idiopathic pulmonary fibrosis model. Structural and kinetic analyses revealed that DWN12088 binds to catalytic site of each protomer of PARS1 dimer in an asymmetric mode with different affinity, resulting in decreased responsiveness at higher doses, thereby expanding safety window. The mutations disrupting PARS1 homodimerization restored the sensitivity to DWN12088, validating negative communication between PARS1 promoters for the DWN12088 binding. Thus, this work suggests that DWN12088, an asymmetric catalytic inhibitor of PARS1 as a novel therapeutic agent against fibrosis with enhanced safety.
Topics: Humans; Amino Acyl-tRNA Synthetases; Fibrosis; Proline; Protein Biosynthesis
PubMed: 37212275
DOI: 10.15252/emmm.202216940 -
Journal of the American Chemical Society Feb 2022Analyzing the δH values in individual amino acids of proteins extracted from vertebrates, we unexpectedly found in some samples, notably bone collagen from seals, more...
Analyzing the δH values in individual amino acids of proteins extracted from vertebrates, we unexpectedly found in some samples, notably bone collagen from seals, more than twice as much deuterium in proline and hydroxyproline residues than in seawater. This corresponds to at least 4 times higher δH than in any previously reported biogenic sample. We ruled out diet as a plausible mechanism for such anomalous enrichment. This finding puts into question the old adage that "you are what you eat".
Topics: Animals; Anseriformes; Bone and Bones; Collagen; Deuterium; Fibroblasts; Humans; Hydroxyproline; Mice; Proline; Seals, Earless; Ursidae
PubMed: 35107291
DOI: 10.1021/jacs.1c12512 -
Cells Apr 2021The accumulation of proline is one of the defense mechanisms of plants against the harmful effects of adverse environmental conditions; however, when pea plants were...
The accumulation of proline is one of the defense mechanisms of plants against the harmful effects of adverse environmental conditions; however, when pea plants were treated for 12 h with CdCl, the proline concentration decreased in the youngest A (not expanded) and B1 (expanded) leaves, and did not change significantly in the B2 (mature, expanded) or C (the oldest) leaves. After 24 h of cadmium (Cd) stress, the proline concentration remained low in A and B1 leaves, while in B2 and C leaves, it increased, and after 48 h, an increase in the proline concentration in the leaves at each stage of development was observed. The role of proline in the different phases of plant response to the Cd treatment is discussed. Changes in proline accumulation corresponded closely with changes in the transcript levels of , a gene encoding D1-pyrroline-5-carboxylate synthetase involved in proline synthesis, and , a gene encoding proline dehydrogenase engaged in proline degradation. CdCl application induced the expression of and , genes encoding proline transporters, especially during the first 12 h of treatment in A and B1 leaves. When the time courses of abscisic acid (ABA) and proline accumulation were compared, it was concluded that an increase in the proline concentration in the leaves of Cd-treated pea plants was more related to a decrease in chlorophyll concentration (leaves B2 and C) and an increase in the malondialdehyde level (A and B1 leaves) than with an increase in ABA concentration alone. Exogenous application of ABA (0.5, 5, 50 µM) significantly increased the proline concentration in the A leaves of pea plants only, and was accompanied by an elevated and repressed expression of and in these leaves, respectively. The presented results suggest that under Cd stress, the accumulation of proline in leaves of pea plants may take place independently of the ABA signaling.
Topics: Abscisic Acid; Base Sequence; Biological Transport; Cadmium; Chlorophyll; Gene Expression Regulation, Plant; Genes, Plant; Malondialdehyde; Pisum sativum; Plant Leaves; Proline; RNA, Messenger; Stress, Physiological
PubMed: 33923901
DOI: 10.3390/cells10040946 -
Biomolecules Jun 2023This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely... (Review)
Review
This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely distributed in nature and are known to enhance the stability of specific secondary structures and/or biological function. Contrary to the ubiquitous DNA-encoded amino acids, the structure and function of these residues are not fully understood. Here, results from experimental and molecular modelling approaches are gathered to classify several classes of non-canonical amino acids according to their ability to induce specific secondary structures yielding different biological functions and improved stability. Regarding side-chain modifications, symmetrical and asymmetrical α,α-dialkyl glycines, Cα to Cα cyclized amino acids, proline analogues, β-substituted amino acids, and α,β-dehydro amino acids are some of the non-canonical representatives addressed. Backbone modifications were also examined, especially those that result in retro-inverso peptidomimetics and depsipeptides. All this knowledge has an important application in the field of peptidomimetics, which is in continuous progress and promises to deliver new biologically active molecules and new materials in the near future.
Topics: Amino Acids; Peptidomimetics; Proline; Amines; Glycine
PubMed: 37371561
DOI: 10.3390/biom13060981 -
Virology Aug 2022Sacbrood virus (SBV) infects larvae of honey bees, resulting in infected larvae becoming fluid-filled sacs. Our previous studies showed that the extract of herbal...
Sacbrood virus (SBV) infects larvae of honey bees, resulting in infected larvae becoming fluid-filled sacs. Our previous studies showed that the extract of herbal medicine, Radix Isatidis, could inhibit Chinese SBV (CSBV) infection in Asian honey bees (Apis cerana). Here, two compounds, adenosine and L-proline, which were previously reported to be associated with immune modulation, were identified in R. Isatidis extract and then selected for an evaluation of their antiviral effect on CSBV infection in A. cerana. Our results revealed that both adenosine and L-proline could significantly mitigate the impact of CSBV on the growth and development of infected larvae and modulate hosts' immune responses by downregulating the expression of immune genes in infected larvae. The results gained from this study suggest that adenosine and L-proline could possibly interfere CSBV infection via immune modulation to avoid exacerbations and nonspecific damage to infected larvae's own tissues.
Topics: Adenosine; Animals; Bees; China; Immunity; Larva; Proline; RNA Viruses; Virus Diseases
PubMed: 35691116
DOI: 10.1016/j.virol.2022.05.008 -
Biomolecules May 2021L-proline (proline) is a key regulator of embryogenesis, placental development, and fetal growth. However, the underlying mechanisms that support the beneficial effects...
L-proline (proline) is a key regulator of embryogenesis, placental development, and fetal growth. However, the underlying mechanisms that support the beneficial effects of proline are largely unknown. This study used porcine trophectoderm cell line 2 (pTr2) to investigate the underlying mechanisms of proline in cell proliferation and redox homeostasis. Cells were cultured in the presence of 0, 0.25, 0.50, or 1.0 mmol/L proline for an indicated time. The results showed that 0.5 and 1.0 mmol/L proline enhanced cell viability. These effects of proline (0.5 mmol/L) were accompanied by the enhanced protein abundance of p-mTORC1, p-p70S6K, p-S6, and p-4E-BP1. Additionally, proline dose-dependently enhanced the mRNA expression of proline transporters [solute carrier family () , , , , and ], elevated proline concentration, and protein abundance of proline dehydrogenase (PRODH). Furthermore, proline addition (0.25 or 0.5 mmol/L) resulted in lower abundance of p-AMPK when compared with a control. Of note, proline resulted in lower reactive oxygen species (ROS) level, upregulated mRNA expression of the catalytic subunit of glutamate-cysteine ligase () and glutathione synthetase (), as well as enhanced total (T)-GSH and GSH concentration when compared with a control. These data indicated that proline activates themTORC1 signaling and modulates the intracellular redox environment via enhancing proline transport.
Topics: Animals; Cell Line; Cell Proliferation; Cell Survival; Embryonic Development; Female; Mechanistic Target of Rapamycin Complex 1; Oxidation-Reduction; Placenta; Pregnancy; Proline; Reactive Oxygen Species; Signal Transduction; Swine
PubMed: 34067570
DOI: 10.3390/biom11050742 -
Natural Product Reports Mar 2020Covering: 1990 to 2019 Many medicinally-relevant compounds are derived from non-ribosomal peptide synthetase (NRPS) products. Type I NRPSs are organized into large... (Review)
Review
Covering: 1990 to 2019 Many medicinally-relevant compounds are derived from non-ribosomal peptide synthetase (NRPS) products. Type I NRPSs are organized into large modular complexes, while type II NRPS systems contain standalone or minimal domains that often encompass specialized tailoring enzymes that produce bioactive metabolites. Protein-protein interactions and communication between the type II biosynthetic machinery and various downstream pathways are critical for efficient metabolite production. Importantly, the architecture of type II NRPS proteins makes them ideal targets for combinatorial biosynthesis and metabolic engineering. Future investigations exploring the molecular basis or protein-protein recognition in type II NRPS pathways will guide these engineering efforts. In this review, we consolidate the broad range of NRPS systems containing type II proteins and focus on structural investigations, enzymatic mechanisms, and protein-protein interactions important to unraveling pathways that produce unique metabolites, including dehydrogenated prolines, substituted benzoic acids, substituted amino acids, and cyclopropanes.
Topics: Amino Acids; Benzoic Acid; Cyclopropanes; Hydroxylation; Lactams; Macrolides; Netropsin; Peptide Synthases; Proline; Protein Interaction Maps; Pyrroles; Thiazoles; Thiones
PubMed: 31593192
DOI: 10.1039/c9np00047j -
Protein Science : a Publication of the... Mar 2024Domains known as von Willebrand factor type D (VWD) are found in extracellular and cell-surface proteins including von Willebrand factor, mucins, and various signaling...
Domains known as von Willebrand factor type D (VWD) are found in extracellular and cell-surface proteins including von Willebrand factor, mucins, and various signaling molecules and receptors. Many VWD domains have a glycine-aspartate-proline-histidine (GDPH) amino-acid sequence motif, which is hydrolytically cleaved post-translationally between the aspartate (Asp) and proline (Pro). The Fc IgG binding protein (FCGBP), found in intestinal mucus secretions and other extracellular environments, contains 13 VWD domains, 11 of which have a GDPH cleavage site. In this study, we investigated the structural and biophysical consequences of Asp-Pro peptide cleavage in a representative FCGBP VWD domain. We found that endogenous Asp-Pro cleavage increases the resistance of the domain to exogenous proteolytic degradation. Tertiary structural interactions made by the newly generated chain termini, as revealed by a crystal structure of an FCGBP segment containing the VWD domain, may explain this observation. Notably, the Gly-Asp peptide bond, upstream of the cleavage site, assumed the cis configuration in the structure. In addition to these local features of the cleavage site, a global organizational difference was seen when comparing the FCGBP segment structure with the numerous other structures containing the same set of domains. Together, these data illuminate the outcome of GDPH cleavage and demonstrate the plasticity of proteins with VWD domains, which may contribute to their evolution for function in a dynamic extracellular environment.
Topics: von Willebrand Factor; Proline; Aspartic Acid; Peptides; Dipeptides
PubMed: 38380729
DOI: 10.1002/pro.4929