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https://www.readbyqxmd.com/read/28943401/crystal-structure-of-l-glutamate-n-acetyltransferase-arga-from-mycobacterium-tuberculosis
#1
Xiuna Yang, Lijie Wu, Yajun Ran, Ao Xu, Bing Zhang, Xiaolin Yang, Rongguang Zhang, Zihe Rao, Jun Li
l-arginine is used as a source of both carbon and nitrogen in Mycobacterium tuberculosis (Mtb) and its biosynthesis is essential for the pathogen's survival. MtbArgA (Rv2747) catalyzes the initial step in l-arginine biosynthesis by transferring an acetyl group from acetyl coenzyme A (AcCoA) to l-glutamate. MtbArgA is a class III N-acetylglutamate synthase (NAGS) with no structural information. Here, we solved the crystal structure of MtbArgA complexed with AcCoA and l-glutamate. The overall structure adopts a classic fold of the GCN5-related N-acetyltransferase (GNAT) family, characterized by a "V"-shaped cleft and β-bulge, but uses distinct residues for the binding and reaction of AcCoA...
September 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918903/saga-is-a-general-cofactor-for-rna-polymerase-ii-transcription
#2
Tiago Baptista, Sebastian Grünberg, Nadège Minoungou, Maria J E Koster, H T Marc Timmers, Steve Hahn, Didier Devys, László Tora
Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA- or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA...
September 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28900165/gcn5l1-modulates-cross-talk-between-mitochondria-and-cell-signaling-to-regulate-foxo1-stability-and-gluconeogenesis
#3
Lingdi Wang, Iain Scott, Lu Zhu, Kaiyuan Wu, Kim Han, Yong Chen, Marjan Gucek, Michael N Sack
The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation...
September 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28887412/enzymatic-modules-of-the-saga-chromatin-modifying-complex-play-distinct-roles-in-drosophila-gene-expression-and-development
#4
Xuanying Li, Christopher W Seidel, Leanne T Szerszen, Jeffrey J Lange, Jerry L Workman, Susan M Abmayr
The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not...
September 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28854355/uv-induced-rpa1-acetylation-promotes-nucleotide-excision-repair
#5
Hanqing He, Jiajia Wang, Ting Liu
Replication protein A (RPA) is a multifunctional, single-stranded DNA-binding protein complex and plays a critical role in DNA replication and damage response. Herein, we show that the 70-kDa subunit of RPA (RPA1) is acetylated on lysine 163 by the acetyltransferases GCN5 and PCAF and that such acetylation is reversed principally via the action of the deacetylase HDAC6. UV irradiation promotes cytoplasmic translocation of HDAC6, thereby disrupting the interaction of HDAC6 with RPA1 and increasing RPA1 acetylation...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28854354/pcaf-gcn5-mediated-acetylation-of-rpa1-promotes-nucleotide-excision-repair
#6
Meimei Zhao, Rui Geng, Xiang Guo, Ruoshi Yuan, Xiao Zhou, Yanyan Zhong, Yanfei Huo, Mei Zhou, Qinjian Shen, Yinglu Li, Weiguo Zhu, Jiadong Wang
The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28756664/structural-and-functional-survey-of-environmental-aminoglycoside-acetyltransferases-reveals-functionality-of-resistance-enzymes
#7
Zhiyu Xu, Peter J Stogios, Andrew T Quaile, Kevin J Forsberg, Sanket Patel, Tatiana Skarina, Scott Houliston, Cheryl Arrowsmith, Gautam Dantas, Alexei Savchenko
Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al...
August 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28751935/chk1-promotes-dna-damage-response-bypass-following-oxidative-stress-in-a-model-of-hydrogen-peroxide-associated-ulcerative-colitis-through-jnk-inactivation-and-chromatin-binding
#8
Kathrin Reissig, Andrew Silver, Roland Hartig, Antje Schinlauer, Diana Walluscheck, Thomas Guenther, Sandra Siedentopf, Jochen Ross, Diep-Khanh Vo, Albert Roessner, Angela Poehlmann-Nitsche
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28741290/biochemical-characterization-of-the-lysine-acetylation-of-tyrosyl-trna-synthetase-in-escherichia-coli
#9
Sumana Venkat, Caroline Gregory, Qinglei Gan, Chenguang Fan
Aminoacyl-tRNA synthetases (aaRSs) play essential roles in protein synthesis. As a member of the aaRS family, the tyrosyl-tRNA synthetase (TyrRS) in Escherichia coli has been shown in proteomic studies to be acetylated at multiple lysine residues. However, these putative acetylation targets have not yet been biochemically characterized. In this study, we applied a genetic-code-expansion strategy to site-specifically incorporate N(ϵ) -acetyl-l-lysine into selected positions of TyrRS for in vitro characterization...
July 24, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#10
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721586/homology-modeling-and-prediction-of-the-amino-acid-residues-participating-in-the-transfer-of-acetyl-coa-to-arylalkylamine-by-the-n-acetyltransferase-from-chryseobacterium-sp
#11
Shinji Takenaka, Takahiro Ozeki, Kosei Tanaka, Ken-Ichi Yoshida
OBJECTIVES: To predict the amino acid residues playing important roles in acetyl-CoA and substrate binding and to study the acetyl group transfer mechanism of Chryseobacterium sp. 5-3B N-acetyltransferase (5-3B NatA). RESULTS: A 3-dimensional homology model of 5-3B NatA was constructed to compare the theoretical structure of this compound with the structures of previously reported proteins belonging to the bacterial GCN5 N-acetyltransferase family. Homology modeling of the 5-3B NatA structure and a characterization of the enzyme's kinetic parameters identified the essential amino acid residues involved in binding and acetyl-group transfer...
July 18, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28710461/bromodomain-factors-of-bet-family-are-new-essential-actors-of-pericentric-heterochromatin-transcriptional-activation-in-response-to-heat-shock
#12
Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, Virginie Faure, Maria Ouzounova, Hector Hernandez-Vargash, Nicolas Reynoird, Sylvain Daujat, Eric Folco, Marc Vigneron, Robert Schneider, André Verdel, Saadi Khochbin, Zdenko Herceg, Cécile Caron, Claire Vourc'h
The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678170/differential-effects-of-histone-acetyltransferase-gcn5-or-pcaf-knockdown-on-urothelial-carcinoma-cells
#13
Evangelia A Koutsogiannouli, Nicholas Wagner, Christiane Hader, Maria Pinkerneil, Michèle J Hoffmann, Wolfgang A Schulz
Disturbances in histone acetyltransferases (HATs) are common in cancers. In urothelial carcinoma (UC), p300 and CBP are often mutated, whereas the GNAT family HATs GCN5 and PCAF (General Control Nonderepressible 5, p300/CBP-Associated Factor) are often upregulated. Here, we explored the effects of specific siRNA-mediated knockdown of GCN5, PCAF or both in four UC cell lines (UCCs). Expression of various HATs and marker proteins was measured by qRT-PCR and western blot. Cellular effects of knockdowns were analyzed by flow cytometry and ATP-, caspase-, and colony forming-assays...
July 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28676112/unusual-acylation-of-chloramphenicol-in-lysobacter-enzymogenes-a-biocontrol-agent-with-intrinsic-resistance-to-multiple-antibiotics
#14
Wei Zhang, Justin Huffman, Shengying Li, Yuemao Shen, Liangcheng Du
BACKGROUND: The environmental gliding bacteria Lysobacter are emerging as a new group of biocontrol agents due to their prolific production of lytic enzymes and potent antibiotic natural products. These bacteria are intrinsically resistant to many antibiotics, but the mechanisms behind the antibiotic resistance have not been investigated. RESULTS: Previously, we have used chloramphenicol acetyltransferase gene (cat) as a selection marker in genetic manipulation of natural product biosynthetic genes in Lysobacter, because chloramphenicol is one of the two common antibiotics that Lysobacter are susceptible to...
July 4, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28674280/interplay-between-chromatin-modulators-and-histone-acetylation-regulates-the-formation-of-accessible-chromatin-in-the-upstream-regulatory-region-of-fission-yeast-fbp1
#15
Akira Adachi, Satoshi Senmatsu, Ryuta Asada, Takuya Abe, Charles S Hoffman, Kunihiro Ohta, Kouji Hirota
Numerous noncoding RNA transcripts are detected in eukaryotic cells. Noncoding RNAs transcribed across gene promoters are involved in the regulation of mRNA transcription via chromatin modulation. This function of noncoding RNA transcription was first demonstrated for the fission yeast fbp1 gene, where a cascade of noncoding RNA transcription events induces chromatin remodeling to facilitate transcription factor binding. We recently demonstrated that the noncoding RNAs from the fbp1 upstream region facilitate binding of the transcription activator Atf1 and thereby promote histone acetylation...
June 30, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#16
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
September 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28642327/declining-histone-acetyltransferase-gcn5-represses-bmsc-mediated-angiogenesis-during-osteoporosis
#17
Huan Jing, Li Liao, Xiaoxia Su, Yi Shuai, Xinjing Zhang, Zhihong Deng, Yan Jin
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs...
June 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28594263/phototrophy-and-starvation-based-induction-of-autophagy-upon-removal-of-gcn5-catalyzed-acetylation-of-atg7-in-magnaporthe-oryzae
#18
Shulin Zhang, Meiling Liang, Naweed I Naqvi, Chaoxiang Lin, Wanqiang Qian, Lian-Hui Zhang, Yi Zhen Deng
Magnaporthe oryzae, the ascomycete fungus that causes rice blast disease, initiates conidiation in response to light when grown on Prune-Agar medium containing both carbon and nitrogen sources. Macroautophagy/autophagy was shown to be essential for M. oryzae conidiation and induced specifically upon exposure to light but is undetectable in the dark. Therefore, it is inferred that autophagy is naturally induced by light, rather than by starvation during M. oryzae conidiation. However, the signaling pathway(s) involved in such phototropic induction of autophagy remains unknown...
August 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28559487/a-toxin-involved-in-salmonella-persistence-regulates-its-activity-by-acetylating-its-cognate-antitoxin-a-modification-reversed-by-cobb-sirtuin-deacetylase
#19
Chelsey M VanDrisse, Anastacia R Parks, Jorge C Escalante-Semerena
Bacterial toxin-antitoxin systems trigger the onset of a persister state by inhibiting essential cellular processes. The TacT toxin of Salmonella enterica is known to induce a persister state in macrophages through the acetylation of aminoacyl-tRNAs. Here, we show that the TacT toxin and the TacA antitoxin work as a complex that modulates TacT activity via the acetylation state of TacA. TacT acetylates TacA at residue K44, a modification that is removed by the NAD(+)-dependent CobB sirtuin deacetylase. TacA acetylation increases the activity of TacT, downregulating protein synthesis...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28559430/acetylation-of-cavin-1-promotes-lipolysis-in-white-adipose-tissue
#20
Shui-Rong Zhou, Liang Guo, Xu Wang, Yang Liu, Wan-Qiu Peng, Yuan Liu, Xiang-Bo Wei, Xin Dou, Meng Ding, Qun-Ying Lei, Shu-Wen Qian, Xi Li, Qi-Qun Tang
White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1...
August 15, 2017: Molecular and Cellular Biology
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