Changes in corticotrope gene expression upon increased expression of peptidylglycine a-amidating monooxygenase, an evolutionarily conserved enzyme
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ABSTRACT:
PROVIDER: PRJNA434597 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6749402_1.fastq.gz | Fastqsanger.gz | |||
| SRR6749402_2.fastq.gz | Fastqsanger.gz | |||
| SRR6749403_1.fastq.gz | Fastqsanger.gz | |||
| SRR6749403_2.fastq.gz | Fastqsanger.gz | |||
| SRR6749404_1.fastq.gz | Fastqsanger.gz |
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Project description:Throughout evolution, secretion has played an essential role in the ability of organisms and single cells to survive in the face of a changing environment. PAM (peptidylglycine a-amidating monooxygenase) is an integral membrane monooxygenase first identified for its role in the biosynthesis of neuroendocrine peptides released by the regulated secretory pathway. By screening for transcripts whose expression in a corticotrope tumor cell line responded to changes in PAM levels, we sought to identify genes not previously known to play a role in secretion. We identified transcription factors, peptidyl prolyl isomerases, endosomal/lysosomal proteins and proteins involved in tissue-specific responses to glucose and amino acid availability that had not previously been recognized as participants in secretion.
2018-05-01 | GSE110809 | GEO
Project description:Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide(TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT), and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic ER stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.
2014-12-19 | GSE64326 | GEO
Project description:Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide(TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT), and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic ER stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation. To identify potential regulators of macrophage reverse cholesterol transport (RCT), liver was isolated from two independent mouse models where the non-biliary RCT pathway known as transintestinal cholesterol excretion (TICE) was either chronically (NPC1L1-liver-transgenic mice) or acutely (ACAT2 antisense oligonucleotide treatment) stimulated. Total RNA was isolated and gene expression levels were profiled on the Affymetrix GeneAtlas MG-430 PM Array Strip (Affymetrix; Santa Clara, CA, USA)
2014-12-19 | E-GEOD-64326 | biostudies-arrayexpress
Project description:Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme-substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme-substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.
| S-EPMC3210774 | biostudies-literature
Project description:To identify evolutionarily conserved Beta-catenin protein interactions, Beta-catenin mRNA from various metazoans was injected into Xenopus embryos and immunopurified at gastrula stage. Beta-catenin complexes were then separated on an SDS-PAGE gel and subjected mass spectrometric analysis
2023-07-08 | PXD035167 | JPOST Repository
Project description:TMEM41B: An Evolutionarily Conserved Nexus in Thermogenic Regulation
| PRJNA1214290 | ENA
Project description:The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized enzyme superfamilies.
| S-EPMC2453236 | biostudies-literature
Project description:The aim of the experiment was to characterise a P450 monooxygenase mutant involved in the biosynthetic pathway of haemolytic saponins. Saponins are a group of glycosidic compounds with an antimicrobial function. The gene CYP716A12 is responsible for an early step in saponin biosythesis. Transcriptome analysis of a CYP716A12 mutant was performed to investigate its function.
2010-12-29 | GSE22835 | GEO
Project description:The aim of the experiment was to characterise a P450 monooxygenase mutant involved in the biosynthetic pathway of haemolytic saponins. Saponins are a group of glycosidic compounds with an antimicrobial function. The gene CYP716A12 is responsible for an early step in saponin biosythesis. Transcriptome analysis of a CYP716A12 mutant was performed to investigate its function. 6 samples were used in the experiment: 3 biological replicates of CYP716A12 mutant plants and 3 biological replicates of wild-type plants.
2010-12-29 | E-GEOD-22835 | biostudies-arrayexpress
Project description:Kynurenine monooxygenase (KMO) knockout mouse liver transcriptomics
| PRJEB62865 | ENA