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S-adenosyl homocysteine

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https://www.readbyqxmd.com/read/28238725/functional-and-structural-analysis-of-programmed-c-methylation-in-the-biosynthesis-of-the-fungal-polyketide-citrinin
#1
Philip A Storm, Dominik A Herbst, Timm Maier, Craig A Townsend
Fungal polyketide synthases (PKSs) are large, multidomain enzymes that biosynthesize a wide range of natural products. A hallmark of these megasynthases is the iterative use of catalytic domains to extend and modify a series of enzyme-bound intermediates. A subset of these iterative PKSs (iPKSs) contains a C-methyltransferase (CMeT) domain that adds one or more S-adenosylmethionine (SAM)-derived methyl groups to the carbon framework. Neither the basis by which only specific positions on the growing intermediate are methylated ("programming") nor the mechanism of methylation are well understood...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28135697/colorimetric-detection-of-endogenous-hydrogen-sulfide-production-in-living-cells
#2
Yong Jin Ahn, Young Ju Lee, Jaemyeon Lee, Doyeon Lee, Hun-Kuk Park, Gi-Ja Lee
Hydrogen sulfide (H2S) has received great attention as a third gaseous signal transmitter, following nitric oxide and carbon monoxide. In particular, H2S plays an important role in the regulation of cancer cell biology. Therefore, the detection of endogenous H2S concentrations within biological systems can be helpful to understand the role of gasotransmitters in pathophysiology. Although a simple and inexpensive method for the detection of H2S has been developed, its direct and precise measurement in living cells remains a challenge...
April 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/27934872/structural-analysis-of-glycine-sarcosine-n-methyltransferase-from-methanohalophilus-portucalensis-reveals-mechanistic-insights-into-the-regulation-of-methyltransferase-activity
#3
Yi-Ru Lee, Te-Sheng Lin, Shu-Jung Lai, Mu-Sen Liu, Mei-Chin Lai, Nei-Li Chan
Methyltransferases play crucial roles in many cellular processes, and various regulatory mechanisms have evolved to control their activities. For methyltransferases involved in biosynthetic pathways, regulation via feedback inhibition is a commonly employed strategy to prevent excessive accumulation of the pathways' end products. To date, no biosynthetic methyltransferases have been characterized by X-ray crystallography in complex with their corresponding end product. Here, we report the crystal structures of the glycine sarcosine N-methyltransferase from the halophilic archaeon Methanohalophilus portucalensis (MpGSMT), which represents the first structural elucidation of the GSMT methyltransferase family...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879050/structural-studies-of-protein-arginine-methyltransferase-2-reveal-its-interactions-with-potential-substrates-and-inhibitors
#4
Vincent Cura, Nils Marechal, Nathalie Troffer-Charlier, Jean-Marc Strub, Matthijs J van Haren, Nathaniel I Martin, Sarah Cianférani, Luc Bonnefond, Jean Cavarelli
PRMT2 is the less-characterized member of the protein arginine methyltransferase family in terms of structure, activity, and cellular functions. PRMT2 is a modular protein containing a catalytic Ado-Met-binding domain and unique Src homology 3 domain that binds proteins with proline-rich motifs. PRMT2 is involved in a variety of cellular processes and has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. PRMT2 has been demonstrated to have weak methyltransferase activity on a histone H4 substrate, but its optimal substrates have not yet been identified...
November 5, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27834681/transient-kinetics-define-a-complete-kinetic-model-for-protein-arginine-methyltransferase-1
#5
Hao Hu, Cheng Luo, Y George Zheng
Protein arginine methyltransferases (PRMTs) are the enzymes responsible for posttranslational methylation of protein arginine residues in eukaryotic cells, particularly within the histone tails. A detailed mechanistic model of PRMT-catalyzed methylation is currently lacking, but it is essential for understanding the functions of PRMTs in various cellular pathways and for efficient design of PRMT inhibitors as potential treatments for a range of human diseases. In this work, we used stopped-flow fluorescence in combination with global kinetic simulation to dissect the transient kinetics of PRMT1, the predominant type I arginine methyltransferase...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27721687/comparative-analyses-of-tomato-yellow-leaf-curl-virus-c4-protein-interacting-host-proteins-in-healthy-and-infected-tomato-tissues
#6
Namgyu Kim, Jinnyun Kim, Bongjun Bang, Inyoung Kim, Hyun-Hee Lee, Jungwook Park, Young-Su Seo
Tomato yellow leaf curl virus (TYLCV), a member of the genus Begomovirus, is one of the most important viruses of cultivated tomatoes worldwide, mainly causing yellowing and curling of leaves with stunting in plants. TYLCV causes severe problems in sub-tropical and tropical countries, as well as in Korea. However, the mechanism of TYLCV infection remains unclear, although the function of each viral component has been identified. TYLCV C4 codes for a small protein involved in various cellular functions, including symptom determination, gene silencing, viral movement, and induction of the plant defense response...
October 2016: Plant Pathology Journal
https://www.readbyqxmd.com/read/27698948/structural-insight-into-binding-mode-of-inhibitor-with-sahh-of-plasmodium-and-human-interaction-of-curcumin-with-anti-malarial-drug-targets
#7
Dev Bukhsh Singh, Seema Dwivedi
S-adenosyl-L-homocysteine hydrolase of Plasmodium falciparum (PfSAHH) is a potential drug target against malaria, and selective inhibition of PfSAHH is the excellent strategy to prevent the growth of parasite inside the host. Therefore, a comparative analysis of human S-adenosyl-L-homocysteine hydrolase (HsSAHH) and PfSAHH has been performed to explore the structural differences. Structural superimposition of PfSAHH and HsSAHH has generated the RMSD of 0.749 Å over 394 alpha carbon pairs. Residues of PfSAHH from position Tyr152 to Lys193 aligned with insertion/deletion region in HsSAHH, and these extra residues results in an extent of variation in cavity region of PfSAHH...
October 2016: Journal of Chemical Biology
https://www.readbyqxmd.com/read/27698120/stimulating-s-adenosyl-l-methionine-synthesis-extends-lifespan-via-activation-of-ampk
#8
Takafumi Ogawa, Ryohei Tsubakiyama, Muneyoshi Kanai, Tetsuya Koyama, Tsutomu Fujii, Haruyuki Iefuji, Tomoyoshi Soga, Kazunori Kume, Tokichi Miyakawa, Dai Hirata, Masaki Mizunuma
Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulating S-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeast Saccharomyces cerevisiae The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27689866/chemical-proteomic-profiling-of-human-methyltransferases
#9
Benjamin D Horning, Radu M Suciu, Darian A Ghadiri, Olesya A Ulanovskaya, Megan L Matthews, Kenneth M Lum, Keriann M Backus, Steven J Brown, Hugh Rosen, Benjamin F Cravatt
Methylation is a fundamental mechanism used in Nature to modify the structure and function of biomolecules, including proteins, DNA, RNA, and metabolites. Methyl groups are predominantly installed into biomolecules by a large and diverse class of S-adenosyl methionine (SAM)-dependent methyltransferases (MTs), of which there are ∼200 known or putative members in the human proteome. Deregulated MT activity contributes to numerous diseases, including cancer, and several MT inhibitors are in clinical development...
October 12, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27624777/inhibition-of-s-adenosylmethionine-dependent-methyltransferase-attenuates-tgf%C3%AE-1-induced-emt-and-metastasis-in-pancreatic-cancer-putative-roles-of-mir-663a-and-mir-4787-5p
#10
Hardik R Mody, Sau Wai Hung, Mohammad AlSaggar, Jazmine Griffin, Rajgopal Govindarajan
The identification of epigenetic reversal agents for use in combination chemotherapies to treat human pancreatic ductal adenocarcinomas (PDAC) remains an unmet clinical need. Pharmacologic inhibitors of Enhancer of Zeste Homolog 2 (EZH2) are emerging as potential histone methylation reversal agents for the treatment of various solid tumors and leukemia; however, the surprisingly small set of mRNA targets identified with EZH2 knockdown suggests novel mechanisms contribute to their antitumorigenic effects. Here, 3-deazaneplanocin-A (DZNep), an inhibitor of S-adenosyl-L-homocysteine hydrolase and EZH2 histone lysine-N-methyltransferase, significantly reprograms noncoding microRNA (miRNA) expression and dampens TGFβ1-induced epithelial-to-mesenchymal (EMT) signals in pancreatic cancer...
November 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27613858/crystal-structure-and-enantioselectivity-of-terpene-cyclization-in-sam-dependent-methyltransferase-tled
#11
Feng Yu, Minjun Li, Chunyan Xu, Bo Sun, Huan Zhou, Zhijun Wang, Qin Xu, Muyun Xie, Gang Zuo, Pei Huang, Haojie Guo, Qisheng Wang, Jianhua He
TleD is an S-adenosyl-L-methionine dependent methyltransferase and acts as one of the key enzymes in the teleocidin B biosynthesis pathway. Besides the methyl transferring, TleD also rearranges the geranyl and indole moiety of the precursor to form a six-membered ring. Moreover, it does not show homologies to any known terpenoid cyclases. In order to elucidate how such a remarkable reaction could be achieved, we determined the complex crystal structures of TleD and the cofactor analogue S-adenosyl-L-homocysteine with or without substrate teleocidin A1...
September 9, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27594595/s-adenosyl-methionine-in-the-therapy-of-depression-and-other-psychiatric-disorders
#12
Nataša Karas Kuželički
Preclinical Research S-adenosyl methionine (SAM) is a major methyl donor and as such exerts its influence on CNS function through methylation reactions, such as methylation of several catecholamine moiety-containing neurotransmitters, epigenetic changes through methylation of DNA, RNA, RNA-binding proteins and histones, and phospholipid methylation. Based on available evidence, SAM is currently recommended as a next-step (second-line) treatment option following inadequate treatment response to a first-line antidepressant...
November 2016: Drug Development Research
https://www.readbyqxmd.com/read/27570878/a-rapid-and-efficient-assay-for-the-characterization-of-substrates-and-inhibitors-of-nicotinamide-n-methyltransferase
#13
Matthijs J van Haren, Javier Sastre Toraño, Davide Sartini, Monica Emanuelli, Richard B Parsons, Nathaniel I Martin
Nicotinamide N-methyltransferase (NNMT) is one of the most abundant small molecule methyltransferases in the human body and is primarily responsible for the N-methylation of the nicotinamide (vitamin B3). Employing the cofactor S-adenosyl-l-methionine, NNMT transfers a methyl group to the pyridine nitrogen of nicotinamide to generate N-methylnicotinamide. Interestingly, NNMT is also able to N-methylate a variety of other pyridine-containing small molecules, suggesting a secondary role for the enzyme in the detoxification of xenobiotics...
September 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27567876/homocysteine-infections-polyamines-oxidative-metabolism-and-the-pathogenesis-of-dementia-and-atherosclerosis
#14
Kilmer S McCully
Hyperhomocysteinemia is a risk factor for development of dementia and Alzheimer's disease (AD), and low blood levels of folate and cobalamin are associated with hyperhomocysteinemia and AD. In elderly subjects with cognitive decline, supplementation with folate, cobalamin, and pyridoxal demonstrated reduction of cerebral atrophy in gray matter regions vulnerable to the AD process. Multiple pathogenic microbes are implicated as pathogenic factors in AD and atherosclerosis, and the deposition of amyloid-β (Aβ), phosphorylation of tau protein, neuronal injury, and apoptosis in AD are secondary to microbial infection...
October 18, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27544050/crystal-structure-of-pentapeptide-independent-chemotaxis-receptor-methyltransferase-cher-reveals-idiosyncratic-structural-determinants-for-receptor-recognition
#15
Monu Batra, Rajesh Sharma, Anjali Malik, Sonali Dhindwal, Pravindra Kumar, Shailly Tomar
Chemotactic methyltransferase, CheR catalyse methylation of specific glutamate residues in the cytoplasmic domain of methyl-accepting chemotactic protein receptors (MCPRs). The methylation of MCPRs is essential for the chemical sensing and chemotactic bacterial mobility towards favorable chemicals or away from unfavorable ones. In this study, crystal structure of B. subtilis CheR (BsCheR) in complex with S-adenosyl-l-homocysteine (SAH) has been determined to 1.8Å resolution. This is the first report of crystal structure belonging to the pentapeptide-independent CheR (PICheR) class...
December 2016: Journal of Structural Biology
https://www.readbyqxmd.com/read/27426303/synthesis-and-anti-hbv-activity-of-%C3%AE-stereoisomer-of-aristeromycin-based-analogs
#16
Mohan Kasula, Masaaki Toyama, Ramakrishnamraju Samunuri, Farhana Rozy, Monika Yadav, Chandralata Bal, Ashok Kumar Jha, Masanori Baba, Ashoke Sharon
The potential antiviral activity of aristeromycin type of derivatives (I) is limited by associated toxicity due to its possible 5'-O-phosphorylation and S-adenosyl-l-homocysteine hydrolase (SAHase) inhibitory activity. Aristeromycin structure has major pharmacophoric motif as 5'-OH and adenosine base, which may have significant role in enzyme binding followed by activity and or toxicity. Thus, the structural optimization to alter this major motif by replacing with its bioisostere and changing the 5'-O conformation through stereochemistry reversal was of interest...
August 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27413346/inhibitor-designing-virtual-screening-and-docking-studies-for-methyltransferase-a-potential-target-against-dengue-virus
#17
Jagbir Singh, Mahesh Kumar, Rani Mansuri, Ganesh Chandra Sahoo, Aakash Deep
AIM: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. INTRODUCTION: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus...
July 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/27355841/convergent-mechanistic-features-between-the-structurally-diverse-n-and-o-methyltransferases-glycine-n-methyltransferase-and-catechol-o-methyltransferase
#18
Jianyu Zhang, Judith P Klinman
Although an enormous and still growing number of biologically diverse methyltransferases have been reported and identified, a comprehensive understanding of the enzymatic methyl transfer mechanism is still lacking. Glycine N-methyltransferase (GNMT), a member of the family that acts on small metabolites as the substrate, catalyzes methyl transfer from S-adenosyl-l-methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and sarcosine. We report primary carbon ((12)C/(14)C) and secondary ((1)H3/(3)H3) kinetic isotope effects at the transferred methyl group, together with (1)H3/(3)H3 binding isotope effects for wild-type GNMT and a series of Tyr21 mutants...
July 27, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27334368/combined-antiparasitic-and-anti-inflammatory-effects-of-the-natural-polyphenol-curcumin-on-turbot-scuticociliatosis
#19
N Mallo, A P DeFelipe, I Folgueira, R A Sueiro, J Lamas, J M Leiro
The histiophagous scuticociliate Philasterides dicentrarchi is the aetiological agent of scuticociliatosis, a parasitic disease of farmed turbot. Curcumin, a polyphenol from Curcuma longa (turmeric), is known to have antioxidant and anti-inflammatory properties. We investigated the in vitro effects of curcumin on the growth of P. dicentrarchi and on the production of pro-inflammatory cytokines in turbot leucocytes activated by parasite cysteine proteases. At 100 μm, curcumin had a cytotoxic effect and completely inhibited the growth of the parasite...
June 23, 2016: Journal of Fish Diseases
https://www.readbyqxmd.com/read/27329856/akmt-catalyzes-extensive-protein-lysine-methylation-in-the-hyperthermophilic-archaeon-sulfolobus-islandicus-but-is-dispensable-for-the-growth-of-the-organism
#20
Yindi Chu, Yanping Zhu, Yuling Chen, Wei Li, Zhenfeng Zhang, Di Liu, Tongkun Wang, Juncai Ma, Haiteng Deng, Zhi-Jie Liu, Songying Ouyang, Li Huang
Protein methylation is believed to occur extensively in creanarchaea. Recently, aKMT, a highly conserved crenarchaeal protein lysine methyltransferase, was identified and shown to exhibit broad substrate specificity in vitro Here, we have constructed an aKMT deletion mutant of the hyperthermophilic crenarchaeon Sulfolobus islandicus The mutant was viable but showed a moderately slower growth rate than the parental strain under non-optimal growth conditions. Consistent with the moderate effect of the lack of aKMT on the growth of the cell, expression of a small number of genes, which encode putative functions in substrate transportation, energy metabolism, transcriptional regulation, stress response proteins, etc, was differentially regulated by more than twofold in the mutant strain, as compared with that in the parental strain...
September 2016: Molecular & Cellular Proteomics: MCP
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