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https://www.readbyqxmd.com/read/28756664/structural-and-functional-survey-of-environmental-aminoglycoside-acetyltransferases-reveals-functionality-of-resistance-enzymes
#1
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
#2
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-lysine-acetylation-of-tyrosyl-trna-synthetase-in-escherichia-coli
#3
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 to be acetylated at multiple lysine residues by proteomic studies. However, these putative acetylation targets have not been biochemically characterized yet. In this study, we applied the genetic code expansion strategy to site-specifically incorporate Nε-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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28642327/declining-histone-acetyltransferase-gcn5-represses-bmsc-mediated-angiogenesis-during-osteoporosis
#11
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
#12
Shulin Zhang, Meiling Liang, Naweed 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...
June 8, 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
#13
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
#14
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
https://www.readbyqxmd.com/read/28541373/the-histone-acetylation-mediated-by-gcn5-regulates-the-hoxc11-gene-expression-in-mefs
#15
Ji Hoon Oh, Ji-Yeon Lee, Kyoung-Ah Kong, Jie Min Kim, Myoung Hee Kim
Hox genes are responsible for encoding transcription factors that are essential for anterior-posterior body patterning at early stages of embryogenesis. However, detailed mechanisms of Hox genes are yet to be defined. Protein kinase B alpha (Akt1) was previously identified as a possible upstream regulator of Hox genes. Furthermore, the Hoxc11 gene has been upregulated in Akt1 null (Akt1-/-) mouse embryonic fibroblasts (MEFs), while repressed in wild-type MEFs. In this study, we propose to investigate the role of Gcn5, a histone acetyltransferase, in the regulation of Hoxc11 expression in MEFs...
May 24, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28539332/identification-and-characterization-of-two-types-of-amino-acid-regulated-acetyltransferases-in-actinobacteria
#16
Yu-Xing Lu, Xin-Xin Liu, Wei-Bin Liu, Bang-Ce Ye
One hundred and fifty GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N- acetyltransferase (GNAT) domain organization have been identified in actinobacteria. The ACT domain is fused to the GNAT domain, conferring amino acid-induced allosteric regulation to these protein acetyltransferases (AAPatA). Members of the AAPatA family share similar secondary structure and are divided into two groups based on the allosteric ligands of the ACT domain: the asparagine-activated PatA and the cysteine-activated PatA...
May 24, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28487409/rice-homeodomain-protein-wox11-recruits-a-histone-acetyltransferase-complex-to-establish-programs-of-cell-proliferation-of-crown-root-meristem
#17
Shaoli Zhou, Wei Jiang, Fei Long, Saifeng Cheng, Wenjing Yang, Yu Zhao, Dao-Xiu Zhou
Shoot-borne crown roots are the major root system in cereals. Previous work has shown that the Wuschel-related homeobox gene WOX11 is necessary and sufficient to promote rice (Oryza sativa) crown root emergence and elongation. Here, we show that WOX11 recruits the ADA2-GCN5 histone acetyltransferase module to activate downstream target genes in crown root meristem. Rice ADA2 and GCN5 genes are highly expressed in root meristem and are shown to be essential for cell division and growth. WOX11 and ADA2-GCN5 commonly target and regulate a set of root-specific genes involved in energy metabolism, cell wall biosynthesis, and hormone response, some of which are known to be important for root development...
May 2017: Plant Cell
https://www.readbyqxmd.com/read/28486510/acetyl-group-coordinated-progression-through-the-catalytic-cycle-of-an-arylalkylamine-n-acetyltransferase
#18
Adam A Aboalroub, Ashleigh B Bachman, Ziming Zhang, Dimitra Keramisanou, David J Merkler, Ioannis Gelis
The transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in driving the ordered formation of binary and ternary complexes remains elusive. Herein, we show that CoA and acetyl-CoA alter the conformation of the substrate binding site of an arylalkylamine N-acetyltransferase (AANAT) to facilitate interaction with acceptor substrates...
2017: PloS One
https://www.readbyqxmd.com/read/28447752/islet-1-induces-the-differentiation-of-mesenchymal-stem-cells-into-cardiomyocyte-like-cells-through-the-regulation-of-gcn5-and-dnmt-1
#19
Qin Yi, Hao Xu, Ke Yang, Yue Wang, Bin Tan, Jie Tian, Jing Zhu
Previous studies from this group demonstrated that insulin gene enhancer binding protein ISL-1 (Islet-1) specifically induces the differentiation of mesenchymal stem cells (MSCs) into cardiomyocyte‑like cells through histone acetylation. However, the underlying mechanisms remain unclear. In the present study, the role of the histone acetylation and DNA methylation on the regulatory mechanism of the Islet‑1 was further investigated by methylation‑specific polymerase chain reaction (PCR), chromatin immunoprecipitation quantitative PCR and western blot analysis...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28445968/usp22-knockdown-enhanced-chemosensitivity-of-hepatocellular-carcinoma-cells-to-5-fu-by-up-regulation-of-smad4-and-suppression-of-akt
#20
Jing Zhang, Nan Luo, Yu Tian, Jiazhi Li, Xiaozhou Yang, Huimin Yin, Congshu Xiao, Jie Sheng, Yang Li, Bo Tang, Rongkuan Li
USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy...
April 11, 2017: Oncotarget
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