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Emel Sahin et al.
Journal of immunotherapy (Hagerstown, Md. : 1997), 42(1), 11-22 (2018-11-09)
Regulatory T cells (Treg cells), a subgroup of CD4 lymphocytes, play a crucial role in serving as an immune suppressor and in maintaining peripheral tolerance. As the accumulation of Treg cells in the tumor microenvironment is significantly associated with a
Tanjing Song et al.
Cell reports, 36(12), 109739-109739 (2021-09-23)
Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli.
C A Jabeena et al.
The Journal of biological chemistry, 296, 100614-100614 (2021-04-12)
Epigenetic modifications have emerged as critical regulators of virulence genes and stage-specific gene expression in Plasmodium falciparum. However, the specific roles of histone core epigenetic modifications in regulating the stage-specific gene expression are not well understood. In this study, we
Cunqi Ye et al.
Molecular cell, 73(6), 1115-1126 (2019-02-18)
Dysregulation of chromatin methylation is associated with defects in cellular differentiation as well as a variety of cancers. How cells regulate the opposing activities of histone methyltransferase and demethylase enzymes to set the methylation status of the epigenome for proper
Lin Huang et al.
Nucleic acids research, 48(13), 7545-7556 (2020-06-11)
While most SAM riboswitches strongly discriminate between SAM and SAH, the SAM/SAH riboswitch responds to both ligands with similar apparent affinities. We have determined crystal structures of the SAM/SAH riboswitch bound to SAH, SAM and other variant ligands at high
Gang Yuan et al.
Nature, 590(7846), 504-508 (2021-02-05)
Amplification of chromosomal region 8p11-12 is a common genetic alteration that has been implicated in the aetiology of lung squamous cell carcinoma (LUSC)1-3. The FGFR1 gene is the main candidate driver of tumorigenesis within this region4. However, clinical trials evaluating
Membrane bound COMT isoform is an interfacial enzyme: general mechanism and new drug design paradigm
Magarkar A, et al.
Chemical Communications (Cambridge, England), 54(28), 3440-3443 (2018)
Kongkai Zhu et al.
Bioorganic chemistry, 81, 289-298 (2018-09-02)
Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as an important therapeutic target for glioblastoma and mantel cell lymphoma. In the present study, 11 novel PRMT5 inhibitors with 5-benzylidene-2-phenylthiazolone scaffold were identified by molecular
Xue Liu et al.
Cell host & microbe, 29(1), 107-120 (2020-10-30)
Streptococcus pneumoniae is an opportunistic human pathogen that causes invasive diseases, including pneumonia, with greater health risks upon influenza A virus (IAV) co-infection. To facilitate pathogenesis studies in vivo, we developed an inducible CRISPR interference system that enables genome-wide fitness testing
Suyin Ge et al.
Toxicology and applied pharmacology, 415, 115450-115450 (2021-02-13)
Eukaryotic translation initiation factor 4E (eIF4E) and protein arginine methyltransferase 5 (PRMT5) are frequently overexpressed in colorectal cancer (CRC) tissues and associated with poor prognosis. Ribavirin, the only clinically approved drug known to target eIF4E, is an anti-viral molecule currently
Daniel Kleiner et al.
Journal of molecular biology, 431(24), 4796-4816 (2019-09-15)
Methionine S-adenosyltransferases (MATs) are predominantly homotetramers, comprised of dimers of dimers. The larger, highly conserved intradimeric interface harbors two active sites, making the dimer the obligatory functional unit. However, functionality of the smaller, more diverged, and recently evolved interdimeric interface
Karin Ortmayr et al.
The Analyst, 140(22), 7687-7695 (2015-10-10)
The sulfur metabolic pathway is involved in basic modes of cellular metabolism, including methylation, cell division, respiratory oscillations and stress responses. Hence, the implicated high reactivity of the sulfur pathway intermediates entails challenges for their quantitative analysis. In particular the
Charlotte A Henderson et al.
Methods (San Diego, Calif.), 167, 39-53 (2019-05-06)
The discovery and engineering of more and more functions of RNA has highlighted the utility of RNA-targeting small molecules. Recently, several fluorogen-binding RNA aptamers have been developed that have been applied to live cell imaging of RNA and metabolites as
S-Adenosylmethionine Rescues Cognitive Deficits in the rTg4510 Animal Model by Stabilizing Protein Phosphatase 2A and Reducing Phosphorylated Tau.
Beauchamp, et al.
Journal of Alzheimer'S Disease, 77, 1705-1715 (2021)
Efrat Resnick et al.
Journal of the American Chemical Society, 141(22), 8951-8968 (2019-05-08)
Covalent probes can display unmatched potency, selectivity, and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening, but such electrophilic fragments were
Simona Selberg et al.
Cell reports, 26(13), 3762-3771 (2019-03-28)
Chemical modifications of RNA provide an additional, epitranscriptomic, level of control over cellular functions. N-6-methylated adenosines (m6As) are found in several types of RNA, and their amounts are regulated by methyltransferases and demethylases. One of the most important enzymes catalyzing
Katalin Módis et al.
Nitric oxide : biology and chemistry, 41, 146-156 (2014-03-29)
Recent data show that colon cancer cells selectively overexpress cystathionine-β-synthase (CBS), which produces hydrogen sulfide (H2S), to maintain cellular bioenergetics, support tumor growth and stimulate angiogenesis and vasorelaxation in the tumor microenvironment. The purpose of the current study was to
Chemical communication between bacteria and cell-free gene expression systems within linear chains of emulsion droplets
Schwarz-Schilling M, et al.
Integrative Biology : Quantitative Biosciences from Nano to Macro, 8(4), 564-570 (2016)
Chun-Min Shan et al.
Cell reports, 35(7), 109137-109137 (2021-05-20)
Oncogenic histone lysine-to-methionine mutations block the methylation of their corresponding lysine residues on wild-type histones. One attractive model is that these mutations sequester histone methyltransferases, but genome-wide studies show that mutant histones and histone methyltransferases often do not colocalize. Using
Yan Zhang et al.
Archives of microbiology, 191(10), 773-783 (2009-09-05)
Enolase-phosphatase (E1), as an enzyme, is involved in methionine salvage pathway in many prokaryotic and eukaryotic organisms. But the identity and function of E1 in Xanthomonas oryzae pv. oryzae (Xoo) remain undetermined. Here, we report the cloning and characterization of
M Zaeem Cader et al.
Cell, 180(2), 278-295 (2020-01-25)
Mutations in FAMIN cause arthritis and inflammatory bowel disease in early childhood, and a common genetic variant increases the risk for Crohn's disease and leprosy. We developed an unbiased liquid chromatography-mass spectrometry screen for enzymatic activity of this orphan protein.
Ted M Lakowski et al.
Analytical biochemistry, 396(1), 158-160 (2009-09-08)
S-Adenosyl-L-homocysteine (AdoHcy) background signal in reactions with protein arginine N-methyltransferase 1 is investigated using an ultrahigh-performance liquid chromatography tandem mass spectrometry assay that measures AdoHcy. We identify three sources of AdoHcy background: enzymatic automethylation, AdoHcy contamination in commercial S-adenosyl-L-methionine (AdoMet)
Andria V Rodrigues et al.
Chembiochem : a European journal of chemical biology, 21(5), 663-671 (2019-09-13)
We recently reported the discovery of phenylacetate decarboxylase (PhdB), representing one of only ten glycyl-radical-enzyme reaction types known, and a promising biotechnological tool for first-time biochemical synthesis of toluene from renewable resources. Here, we used experimental and computational data to
Silvia Giatti et al.
Journal of medicinal chemistry, 64(8), 4553-4566 (2021-04-13)
Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a
Guillermo A Senisterra et al.
Journal of biomolecular screening, 15(3), 314-320 (2010-02-13)
Protein stabilization upon ligand binding has frequently been used to identify ligands for soluble proteins. Methods such as differential scanning fluorimetry (DSF) and differential static light scattering (DSLS) have been employed in the 384-well format and have been useful in
Seishu Gen et al.
Biochemical and biophysical research communications, 541, 84-89 (2021-01-23)
Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein that is partially regulated by insulin, energy, oxygen, and growth factors. Mutations in the TSC2 gene and loss of TSC2 promote cell growth by the mammalian target of rapamycin complex 1
Xiaofan Yang et al.
Frontiers in immunology, 12, 745784-745784 (2021-10-08)
Antiretroviral drugs effectively halt HIV-1 replication and disease progression, however, due to the presence of a stable viral latent reservoir, the infection cannot be cured by antiretroviral drugs alone. Elucidating the molecular mechanisms underlying HIV-1 latent infection remains a critical
Jacob L Litke et al.
Nature biotechnology, 37(6), 667-675 (2019-04-10)
RNA aptamers and RNA aptamer-based devices can be genetically encoded and expressed in cells to probe and manipulate cellular function. However, their usefulness in the mammalian cell is limited by low expression and rapid degradation. Here we describe the Tornado
Yaping Wang et al.
Plant physiology and biochemistry : PPB, 149, 121-131 (2020-02-18)
Flower senescence is classified into ethylene-dependent and ethylene-independent manners and determines the flower longevity which is valuable for ornamental plants. However, the manner of petal senescence in tulip is still less defined. In this study, we characterized the physiological indexes
Alice Migazzi et al.
Cell reports, 35(2), 108980-108980 (2021-04-15)
The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated HTT and
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