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https://www.readbyqxmd.com/read/29350227/albusnodin-an-acetylated-lasso-peptide-from-streptomyces-albus
#1
Chuhan Zong, Wai Ling Cheung-Lee, Hader E Elashal, Monika Raj, A James Link
We describe a lasso peptide, albusnodin, that is post-translationally modified with an acetyl group, the first example of a lasso peptide with this modification. Using heterologous expression, we further show that the acetyltransferase colocalized with the albusnodin gene cluster is required for the biosynthesis of this lasso peptide. This type of lasso peptide is widespread in Actinobacteria with 44 examples found in currently sequenced genomes.
January 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#2
Michael R Michaelides, Arthur Kluge, Michael Patane, John H Van Drie, Ce Wang, T Matthew Hansen, Roberto M Risi, Robert Mantei, Carmen Hertel, Kannan Karukurichi, Alexandre Nesterov, David McElligott, Peter de Vries, J William Langston, Philip A Cole, Ronen Marmorstein, Hong Liu, Loren Lasko, Kenneth D Bromberg, Albert Lai, Edward A Kesicki
p300 and its paralog CBP can acetylate histones and other proteins and have been implicated in a number of diseases characterized by aberrant gene activation, such as cancer. A novel, highly selective, orally bioavailable histone acetyltransferase (HAT) domain inhibitor has been identified through virtual ligand screening and subsequent optimization of a unique hydantoin screening hit. Conformational restraint in the form of a spirocyclization followed by substitution with a urea led to a significant improvement in potency...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348522/in-vitro-and-in-vivo-antimicrobial-activity-of-ts2037-a-novel-aminoglycoside-antibiotic
#3
Yoko Hirai, Kazunori Maebashi, Hideki Fushimi, Yukiko Hiraiwa, Shoichi Murakami, Takayuki Usui, Yoshihisa Akiyama, Nobuto Minowa, Daishiro Ikeda
To overcome serious methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections, we synthesized TS2037, 5,4″-diepi-arbekacin, a novel aminoglycoside antibiotic, and evaluated its biological properties. TS2037 showed broad-range, as well as robust antibacterial activities against Gram-positive and Gram-negative bacteria. The MIC50 and MIC90 of TS2037 against clinical isolates of MRSA (n = 54) were both 0.25 µg/mL, and no resistant strain was observed. The MIC50 and MIC90 of TS2037 against clinical isolates of P...
January 18, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29345920/acetylation-by-eis-and-deacetylation-by-rv1151c-of-mycobacterium-tuberculosis-hupb-biochemical-and-structural-insight
#4
Keith D Green, Tapan Biswas, Allan H Pang, Melisa J Willby, Matthew S Reed, Olga Stuchlik, Jan Pohl, James E Posey, Oleg V Tsodikov, Sylvie Garneau-Tsodikova
Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity and chromosome maintenance. Post-translational modifications of bacterial NAPs appear to function similarly to their better studied mammalian counterparts. The histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously observed to be acetylated by the acetyltransferase Eis, leading to genome reorganization. We report biochemical and structural aspects of acetylation of HupB by Eis. We also found that the SirT-family NAD+-dependent deacetylase Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation kinetics...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29343473/smoking-affects-the-interferon-beta-treatment-response-in-multiple-sclerosis
#5
Eva R Petersen, Annette B Oturai, Nils Koch-Henriksen, Melinda Magyari, Per S Sørensen, Finn Sellebjerg, Helle B Søndergaard
OBJECTIVE: To investigate whether smoking in patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFN-β) is associated with the relapse rate and whether there is an interaction between smoking and human leukocyte antigen (HLA)-DRB1*15:01, HLA-A*02:01, and the N-acetyltransferase-1 (NAT1) variant rs7388368A. METHODS: DNA from 834 IFN-β-treated patients with RRMS from the Danish Multiple Sclerosis Biobank was extracted for genotyping...
January 17, 2018: Neurology
https://www.readbyqxmd.com/read/29342871/interferons-reprogramming-the-metabolic-network-against-viral-infection
#6
REVIEW
Kavita Raniga, Chen Liang
Viruses exploit the host and induce drastic metabolic changes to ensure an optimal environment for replication and the production of viral progenies. In response, the host has developed diverse countermeasures to sense and limit these alterations to combat viral infection. One such host mechanism is through interferon signaling. Interferons are cytokines that enhances the transcription of hundreds of interferon-stimulated genes (ISGs) whose products are key players in the innate immune response to viral infection...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29341588/human-neuraminidase-isoenzymes-show-variable-activities-for-9-o-acetyl-sialoside-substrates
#7
Carmanah D Hunter, Neha Khanna, Michele R Richards, Reza Rezaei Darestani, Chunxia Zou, John S Klassen, Christopher W Cairo
Recognition of terminal sialic acids is central to many cellular processes, and structural modification of sialic acid can disrupt these interactions. A prominent, naturally occuring, modification of sialic acid is 9-O-acetylation (9-O-Ac). Study of this modification through generation and analysis of 9-O-Ac sialosides is challenging due to the lability of the acetate group. Fundamental questions regarding the role of 9-O-Ac sialic acids remain unanswered, including what effect it may have on recognition and hydrolysis by the human neuraminidase enzymes (hNEU)...
January 17, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29339455/high-n-acetyltransferase-1-nat1-expression-is-associated-with-estrogen-receptor-expression-in-breast-tumors-but-is-not-under-direct-regulation-by-estradiol-17beta-diol-or-dihydrotestosterone-in-breast-cancer-cells
#8
Xiaoyan Zhang, Samantha M Carlisle, Mark A Doll, Robert C G Martin, J Christopher States, Carolyn M Klinge, David W Hein
N-acetyltransferase 1 (NAT1) is an enzyme which metabolizes carcinogens suggesting a potential role in breast carcinogenesis. High NAT1 expression in breast tumors is associated with estrogen receptor α (ERα+) and the luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme activity were higher in human breast tumors with high expression of ERα/ESR1 compared to normal breast tissue. There was a strong correlation between NATb promoter and NAT1 protein expression/enzyme activity. High NAT1 expression in tumors was not due to adipocytes as evidenced by low PLIN expression...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29339447/guidance-of-super-enhancers-in-regulation-of-il-9-induction-and-airway-inflammation
#9
Xiang Xiao, Yihui Fan, Junhui Li, Xiaolong Zhang, Xiaohua Lou, Yaling Dou, Xiaomin Shi, Peixiang Lan, Yue Xiao, Laurie Minze, Xian Chang Li
Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29336305/inferring-joint-sequence-structural-determinants-of-protein-functional-specificity
#10
Andrew F Neuwald, L Aravind, Stephen F Altschul
Residues responsible for allostery, cooperativity, and other subtle but functionally important interactions remain difficult to detect. To aid such detection, we employ statistical inference based on the assumption that residues distinguishing a protein subgroup from evolutionarily divergent subgroups often constitute an interacting functional network. We identify such networks with the aid of two measures of statistical significance. One measure aids identification of divergent subgroups based on distinguishing residue patterns...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29335245/cdk9-mediated-phosphorylation-controls-the-interaction-of-tip60-with-the-transcriptional-machinery
#11
Prisca Brauns-Schubert, Florian Schubert, Manuela Wissler, Martina Weiss, Lisa Schlicher, Simon Bessler, Mariam Safavi, Cornelius Miething, Christoph Borner, Tilman Brummer, Ulrich Maurer
The acetyltransferase TIP60 is regulated by phosphorylation, and we have previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53-mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3 requires a priming phosphorylation on S90, and here, we identify CDK9 as a TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant, TIP60S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II, while its association with the TIP60 complex subunit EPC1 is not affected...
January 15, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29332244/structural-insights-into-the-function-of-elongator
#12
REVIEW
Udit Dalwadi, Calvin K Yip
Conserved from yeast to humans, Elongator is a protein complex implicated in multiple processes including transcription regulation, α-tubulin acetylation, and tRNA modification, and its defects have been shown to cause human diseases such as familial dysautonomia. Elongator consists of two copies of six core subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in size. Although the catalytic subunit of Elongator is Elp3, which contains a radical S-adenosyl-L-methionine (SAM) domain and a putative histone acetyltransferase domain, the Elp4/5/6 subcomplex also possesses ATP-modulated tRNA binding activity...
January 13, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29328619/characterization-of-the-polyspecific-transferase-of-murine-type-i-fatty-acid-synthase-fas-and-implications-for-polyketide-synthase-pks-engineering
#13
Alexander Rittner, Karthik S Paithankar, Khanh Vu Huu, Martin Grininger
Fatty acid synthases (FASs) and polyketide synthases (PKSs) condense acyl compounds to fatty acids and polyketides, respectively. Both, FASs and PKSs, harbor acyltransferases (ATs), which select substrates for condensation by β-ketoacyl synthases (KSs). Here, we present the structural and functional characterization of the polyspecific malonyl/acetyltransferase (MAT) of murine FAS. We assign kinetic constants for the transacylation of the native substrates, acetyl- and malonyl-CoA, and demonstrate the promiscuity of FAS to accept structurally and chemically diverse CoA-esters...
January 12, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29327125/icariin-improves-cognitive-impairment-after-traumatic-brain-injury-by-enhancing-hippocampal-acetylation
#14
Zi-Gang Zhang, Xin Wang, Jin-Hai Zai, Cai-Hua Sun, Bing-Chun Yan
OBJECTIVE: To examine the effect of icariin (ICA) on the cognitive impairment induced by traumatic brain injury (TBI) in mice and the underlying mechanisms related to changes in hippocampal acetylation level. METHODS: The modifified free-fall method was used to establish the TBI mouse model. Mice with post-TBI cognitive impairment were randomly divided into 3 groups using the randomised block method (n=7): TBI (vehicle-treated), low-dose (75 mg/kg) and high-dose (150 mg/kg) of ICA groups...
January 9, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29323231/mice-deficient-in-the-shmt2-gene-have-mitochondrial-respiration-defects-and-are-embryonic-lethal
#15
Haruna Tani, Sakiko Ohnishi, Hiroshi Shitara, Takayuki Mito, Midori Yamaguchi, Hiromichi Yonekawa, Osamu Hashizume, Kaori Ishikawa, Kazuto Nakada, Jun-Ichi Hayashi
Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for human aging and age-associated mitochondrial respiration defects. However, our previous findings suggested an alternative hypothesis of human aging-that epigenetic changes but not mutations regulate age-associated mitochondrial respiration defects, and that epigenetic downregulation of nuclear-coded genes responsible for mitochondrial translation [e.g., glycine C-acetyltransferase (GCAT), serine hydroxymethyltransferase 2 (SHMT2)] is related to age-associated respiration defects...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321817/enhanced-myc-association-with-the-nua4-histone-acetyltransferase-complex-mediated-by-the-adenovirus-e1a-n-terminal-domain-activates-a-subset-of-myc-target-genes-highly-expressed-in-cancer-cells
#16
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The proto-oncogene MYC is a transcription factor over-expressed in many cancers and required for cell survival. Its function is regulated by histone acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60 complex. However, the roles of the HAT complexes during MYC function in cancer have not been well characterized. We recently showed that adenovirus E1A and its N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4 complex...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29321206/revealing-the-protein-propionylation-activity-of-the-histone-acetyltransferase-males-absent-on-the-first-mof
#17
Zhen Han, Hong Wu, Sunjoo Kim, Xiangkun Yang, Qianjin Li, He Huang, Houjian Cai, Michael G Bartlett, Aiping Dong, Hong Zeng, Peter J Brown, Xiangjiao Yang, Cheryl H Arrowsmith, Yingming Zhao, Y George Zheng
Short-chain acylation of lysine residues recently emerges as a group of reversible posttranslational modifications in mammalian cells. The diversity of acylation further broadens the landscape and complexity of the proteome. Identification of regulatory enzymes and effector proteins for lysine acylation is critical to understand functions of these novel modifications at the molecular level. Here, we report that the MYST family of lysine acetyltransferases (KATs) possesses strong propionyltransferase activity both in vitro and in cellulo...
January 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29321169/the-actin-mrtf-srf-transcriptional-circuit-controls-tubulin-acetylation-via-%C3%AE-tat1-gene-expression
#18
Jaime Fernández-Barrera, Miguel Bernabé-Rubio, Javier Casares-Arias, Laura Rangel, Laura Fernández-Martín, Isabel Correas, Miguel A Alonso
The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)-dependent transcription, which is known to be repressed by increased levels of G-actin...
January 10, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29319543/choline-acetyltransferase-and-trka-expression-as-well-as-the-improvement-in-cognition-produced-by-e2-and-p4-in-ovariectomized-rats-are-blocked-by-ici-182%C3%A2-780-and-ru486
#19
Judith Espinosa-Raya, Ulises Cruz-Raya, Margarita López-Martínez, Ofir Picazo
Treatment with 17-β estradiol and progesterone improves the performance of ovariectomized rats in an autoshaping learning task, representing cognitive improvement. To test whether this is attributable to genomic mechanisms, the antiestrogen ICI 182 780 or antiprogesterone RU486 was injected into ovariectomized animals primed previously with estrogen or progesterone, respectively. Compared with the vehicle control, each hormone administered alone produced an elevated expression of choline acetyltransferase and TrkA, along with an improvement in performance on the behavioral test...
January 9, 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29317496/a-functional-link-between-nad-homeostasis-and-n-terminal-protein-acetylation-in-saccharomyces-cerevisiae
#20
Trevor Croft, Christol James Theoga Raj, Michelle Salemi, Brett S Phinney, Su-Ju Lin
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite participating in cellular redox chemistry and signaling, and the complex regulation of NAD+ metabolism is not yet fully understood. To investigate this, we established a NAD+-intermediate specific reporter system to identify factors required for salvage of metabolically-linked nicotinamide (NAM) and nicotinic acid (NA). Mutants lacking components of the NatB complex, NAT3 and MDM20, appeared as hits in this screen. NatB is an Nα-terminal-acetyltransferase responsible for acetylation of the amino terminus of specific Met-retained peptides...
January 9, 2018: Journal of Biological Chemistry
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