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Gregory R Wagner et al.
Molecular cell, 54(1), 5-16 (2014-04-15)
Cellular proteins are decorated with a wide range of acetyl and other acyl modifications. Many studies have demonstrated regulation of site-specific acetylation by acetyltransferases and deacetylases. Acylation is emerging as a new type of lysine modification, but less is known
Panagis Filippakopoulos et al.
Nature reviews. Drug discovery, 13(5), 337-356 (2014-04-23)
Lysine acetylation is a key mechanism that regulates chromatin structure; aberrant acetylation levels have been linked to the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are small interaction modules found on diverse proteins, some of
Luciana R Mazzitelli et al.
The Journal of biological chemistry, 289(15), 10761-10768 (2014-03-04)
The transport of calcium to the extracellular space carried out by plasma membrane Ca(2+) pumps (PMCAs) is essential for maintaining low Ca(2+) concentrations in the cytosol of eukaryotic cells. The activity of PMCAs is controlled by autoinhibition. Autoinhibition is relieved
Atsuko Ueki et al.
Archives of microbiology, 197(1), 97-104 (2014-12-03)
A strictly anaerobic bacterial strain (WN037(T)) was isolated from a methanogenic reactor. Cells were Gram-positive rods. Strain WN037(T) was asaccharolytic. The strain fermented L-lysine in the presence of B-vitamin mixture or vitamin B12 and produced acetate and butyrate. L-arginine and
Kaihang Wang et al.
Nature chemistry, 6(5), 393-403 (2014-04-24)
The ability to introduce different biophysical probes into defined positions in target proteins will provide powerful approaches for interrogating protein structure, function and dynamics. However, methods for site-specifically incorporating multiple distinct unnatural amino acids are hampered by their low efficiency.
Wei Wan et al.
Biochimica et biophysica acta, 1844(6), 1059-1070 (2014-03-19)
The genetic incorporation of the 22nd proteinogenic amino acid, pyrrolysine (Pyl) at amber codon is achieved by the action of pyrrolysyl-tRNA synthetase (PylRS) together with its cognate tRNA(Pyl). Unlike most aminoacyl-tRNA synthetases, PylRS displays high substrate side chain promiscuity, low
Yuanyuan Jiang et al.
Journal of molecular biology, 426(20), 3413-3425 (2014-03-07)
Estrogen receptor (ER) signaling plays a pivotal role in many developmental processes and has been implicated in numerous diseases including cancers. We recently showed that direct ERα methylation by the multi-specificity histone lysine methyltransferase SMYD2 regulates estrogen signaling through repressing
Muhammad Zoabi et al.
Nucleic acids research, 42(21), 13026-13038 (2014-11-08)
The JmjC-containing lysine demethylase, KDM4D, demethylates di-and tri-methylation of histone H3 on lysine 9 (H3K9me3). How KDM4D is recruited to chromatin and recognizes its histone substrates remains unknown. Here, we show that KDM4D binds RNA independently of its demethylase activity.
Paul A Del Rizzo et al.
Biochimica et biophysica acta, 1839(12), 1404-1415 (2014-06-21)
Lysine methylation has emerged as a prominent covalent modification in histones and non-histone proteins. This modification has been implicated in numerous genomic processes, including heterochromatinization, cell cycle progression, DNA damage response, DNA replication, genome stability, and epigenetic gene regulation that
Nathan R Rose et al.
Biochimica et biophysica acta, 1839(12), 1362-1372 (2014-02-25)
DNA methylation acts as an epigenetic modification in vertebrate DNA. Recently it has become clear that the DNA and histone lysine methylation systems are highly interrelated and rely mechanistically on each other for normal chromatin function in vivo. Here we
Jiamu Du et al.
Biochimica et biophysica acta, 1839(8), 719-727 (2014-04-22)
Epigenetic mechanisms control gene regulation by writing, reading and erasing specific epigenetic marks. Within the context of multi-disciplinary approaches applied to investigate epigenetic regulation in diverse systems, structural biology techniques have provided insights at the molecular level of key interactions
Mariam Traoré et al.
Organic letters, 16(13), 3588-3591 (2014-06-25)
Aza-peptides with basic amino acid residues (lysine, ornithine, arginine) and derivatives were synthesized by an effective approach featuring alkylation of a hydrazone-protected aza-glycine residue with α-bromo ω-chloro propane and butane to provide the corresponding alkyl chloride side chains. Displacement of
Audrey Letourneau et al.
Nature, 508(7496), 345-350 (2014-04-18)
Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of
C Derek Ma et al.
Nature, 517(7534), 347-350 (2015-01-17)
The structure of water near non-polar molecular fragments or surfaces mediates the hydrophobic interactions that underlie a broad range of interfacial, colloidal and biophysical phenomena. Substantial progress over the past decade has improved our understanding of hydrophobic interactions in simple
Rakhi Gupta et al.
Developmental biology, 395(1), 38-49 (2014-09-11)
To determine the hierarchy of transcriptional regulation within the in vivo vertebrate embryo, we examined whether developmental enhancers were influenced by Nodal signaling during early embryogenesis in Xenopus tropicalis. We find that developmental enhancers, defined by the active enhancer chromatin
Keisuke Miyagawa et al.
Proceedings of the National Academy of Sciences of the United States of America, 111(16), 5950-5955 (2014-04-09)
Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by
Li Jiao et al.
The American journal of clinical nutrition, 101(1), 126-134 (2014-12-21)
Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes.
Francesca Mattiroli et al.
Nature structural & molecular biology, 21(4), 308-316 (2014-04-05)
Ubiquitin and ubiquitin-like modifications are central to virtually all cellular signaling pathways. They occur primarily on lysine residues of target proteins and stimulate a large number of downstream signals. The diversity of these signals depends on the type, location and
Panagiotis Ntziachristos et al.
Nature, 514(7523), 513-517 (2014-08-19)
T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic
Jennifer C Harr et al.
The Journal of cell biology, 208(1), 33-52 (2015-01-07)
Nuclear organization has been implicated in regulating gene activity. Recently, large developmentally regulated regions of the genome dynamically associated with the nuclear lamina have been identified. However, little is known about how these lamina-associated domains (LADs) are directed to the
Methylation: a multifaceted modification - looking at transcription and beyond.
Johnathan R Whetstine
Biochimica et biophysica acta, 1839(12), 1351-1352 (2014-09-17)
Jean-Sébastien Jouhanneau et al.
Neuron, 84(5), 1065-1078 (2014-12-03)
Neighboring cortical excitatory neurons show considerable heterogeneity in their responses to sensory stimulation. We hypothesized that a subset of layer 2 excitatory neurons in the juvenile (P18 to 27) mouse whisker somatosensory cortex, distinguished by expression of the activity-dependent fosGFP
Catherine A Musselman et al.
Biochimica et biophysica acta, 1839(8), 686-693 (2014-04-15)
Lysine methylation is the most versatile covalent posttranslational modification (PTM) found in histones and non-histone proteins. Over the past decade a number of methyllysine-specific readers have been discovered and their interactions with histone tails have been structurally and biochemically characterized.
Anna Cascante et al.
Journal of molecular biology, 426(20), 3467-3477 (2014-04-22)
Neural stem cell (NSC) state and fate depend on spatially and temporally synchronized transcriptional and epigenetic regulation of the expression of extrinsic signaling factors and intrinsic cell-specific genes, but the functional roles for chromatin-modifying enzymes in neural differentiation remain poorly
Takashi Toyama et al.
Chemico-biological interactions, 214, 41-48 (2014-03-04)
Covalent modification of cellular proteins by electrophiles affects electrophilic signal transduction and the dysfunction of enzymes that is involved in cytotoxicity. We have recently found a unique reaction which restores glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that has been modified by 1,2-naphthoquinone (1,2-NQ)
Thomas Kusch et al.
Proceedings of the National Academy of Sciences of the United States of America, 111(13), 4850-4855 (2014-03-19)
Histone H3 lysine 4 trimethylation (H3K4me3) and the acetylated H2A variant, H2A.Z/v (H2Avac), are enriched at promoters of highly transcribed loci including the stress response genes. Using the inducible Drosophila hsp70 loci as a model, we study here the roles
Sun-Shin Cha et al.
Biochemical and biophysical research communications, 450(2), 1045-1050 (2014-07-01)
MurF adds d-Ala-d-Ala dipeptide to UDP-N-acetylmuramyl-l-Ala-γ-d-Glu-m-DAP (or l-Lys) in an ATP-dependent manner, which is the last step in the biosynthesis of monomeric precursor of peptidoglycan. Here we report crystal structures of two MurF-ATP complexes: the MurF-ATP complex and the MurF-ATP-UDP
Binuraj R K Menon et al.
The Journal of biological chemistry, 289(49), 34161-34174 (2014-09-13)
Cobalamin-dependent enzymes enhance the rate of C-Co bond cleavage by up to ∼10(12)-fold to generate cob(II)alamin and a transient adenosyl radical. In the case of the pyridoxal 5'-phosphate (PLP) and cobalamin-dependent enzymes lysine 5,6-aminomutase and ornithine 4,5 aminomutase (OAM), it
Cuylar J T Conly et al.
Biochemistry, 53(47), 7396-7406 (2014-11-05)
Dihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and plants, controls a critical step in the biosynthesis of l-lysine and meso-diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS catalyzes the condensation of pyruvate and (S)-aspartate-β-semialdehyde, forming an unstable
Timothy J Stasevich et al.
Nature, 516(7530), 272-275 (2014-09-26)
In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation, a variety of residue-specific modifications have now been linked to RNA polymerase II (RNAP2) activity, but it remains unclear if
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