Article
Cell Biology
Takafumi Ogawa, Koji Masumura, Yuki Kohara, Muneyoshi Kanai, Tomoyoshi Soga, Yoshikazu Ohya, T. Keith Blackwell, Masaki Mizunuma
Summary: Methionine restriction can extend lifespan and delay aging-associated pathologies. Supplementation with S-adenosyl-L-homocysteine (SAH) can mimic the effects of methionine restriction by reducing methionine levels and activating AMP-activated protein kinase (AMPK), thereby extending lifespan.
Article
Biochemistry & Molecular Biology
Robina Scheuer, Theresa Dietz, Jonas Kretz, Lydia Hadjeras, Matthew McIntosh, Elena Evguenieva-Hackenberg
Summary: In Sinorhizobium meliloti, the SAM-II riboswitches preceding the methionine biosynthesis genes metA and metZ regulate their expression through different mechanisms. Structural changes in the riboswitch cause transcriptional termination and generate sRNAs. A putative terminator and codon downstream of the metA riboswitch may contribute to metA regulation. Under high SAM conditions, sRNA levels increase, and mRNA levels decrease, while both are stabilized. The Shine-Dalgarno sequence and AUG2 codon play important roles in metA translation, and riboswitch binding sequesters the SD sequence, stabilizing the mRNA, thereby achieving RNA-based regulation.
Article
Multidisciplinary Sciences
Muriel Dresen, Desiree Schaaf, Jesus Arenas, Astrid de Greeff, Peter Valentin-Weigand, Andreas Nerlich
Summary: A study identified TrpX gene as a potential tryptophan/tyrosine transport system substrate-binding protein in Streptococcus suis. It was found that TrpX is crucial for tryptophan uptake and bacterial growth. TrpX is part of an operon structure and regulated by a tryptophan T-box riboswitch.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Yu-Hsuan Lee, Daan Ren, Byungsun Jeon, Hung-wen Liu
Summary: This review summarizes recent advances in the study of S-adenosyl-l-methionine (SAM) utilizing enzymes. SAM is a naturally occurring molecule that is commonly associated with methyltransfer reactions. However, it has been found that SAM can also donate other moieties during natural product biosynthetic reactions. The review focuses on the discovery of novel SAM utilizing enzymes and the role of SAM in sulfonium chemistry.
NATURAL PRODUCT REPORTS
(2023)
Article
Cell Biology
Xinquan Zhang, Wen Meng, Jian Feng, Xinghong Gao, Chao Qin, Pinghui Feng, Yufei Huang, Shou-Jiang Gao
Summary: This study identifies the suppressive role of RNA methyltransferase METTL16 in KSHV lytic replication. METTL16 regulates the SAM cycle to maintain intracellular SAM level and redox homeostasis, thereby inhibiting KSHV lytic replication.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Mangal S. Kadam, V. L. S. Prasad Burra
Summary: Methylation plays a significant role in various diseases, and methyltransferases are important targets for drug development. However, the function of methyltransferases relies on the presence of SAM. This article provides a comprehensive analysis of SAM-receptor interactions and reveals crucial insights into the structure and function of SAM.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Nutrition & Dietetics
Hammad Ullah, Ayesha Khan, Kannan R. R. Rengasamy, Alessandro Di Minno, Roberto Sacchi, Maria Daglia
Summary: Depression is a prevalent and serious health issue globally, and current treatment options are limited. SAMe and probiotics have shown potential therapeutic roles in depression by regulating microbial imbalance and reducing inflammation.
Article
Multidisciplinary Sciences
Surajit Chatterjee, Adrien Chauvier, Shiba S. Dandpat, Irina Artsimovitch, Nils G. Walter
Summary: In bacteria, the interaction between RNA polymerase and ribosome regulates gene expression through transcription-translation coupling. This coupling is mainly achieved by RNA polymerase promoting the binding of the ribosomal 30S subunit to antagonize ribosome binding site occlusion induced by a riboswitch, thereby facilitating translation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Changqing Wu, Yu'e Liu, Wenju Liu, Tianhui Zou, Shaojuan Lu, Chengjie Zhu, Le He, Jie Chen, Lan Fang, Lin Zou, Ping Wang, Lihong Fan, Hongxiang Wang, Han You, Juxiang Chen, Jing-Yuan Fang, Cizhong Jiang, Yufeng Shi
Summary: This study identified the NNMT-DNMT1 axis as a critical molecular mechanism determining cancer cell sensitivity to OXPHOS inhibition, and revealed NNMT and DNMT1 as reliable biomarkers for OXPHOS-targeting cancer therapies.
Article
Biochemistry & Molecular Biology
Marta Robledo, Natalia I. Garcia-Tomsig, Ana M. Matia-Gonzalez, Fernando M. Garcia-Rodriguez, Jose I. Jimenez-Zurdo
Summary: This study captured the interactions between three trans-sRNAs regulating nutrient uptake and cell cycle in Sinorhizobium meliloti through affinity chromatography, revealing a wide range of proteins associated with sRNAs and their functions. Particularly, the finding of MetK as a reliable binding partner of these sRNAs highlights a broad specificity for RNA binding as an unprecedented feature of this housekeeping prokaryotic enzyme.
Article
Biochemistry & Molecular Biology
Chenqi Cao, Kaili Nie, Haijun Xu, Luo Liu
Summary: S-adenosyl-L-methionine (SAM) is an active form of methionine that plays a crucial role in various metabolic reactions. Methionine adenosyltransferase (MAT) is the enzyme responsible for the production of SAM from methionine and ATP. However, the lack of an efficient method for high-throughput detection of SAM has hindered directed evolution studies of MAT. In this study, a colorimetric method for directed evolution of MAT was established, leading to the discovery of variant I303V/Q22R with significantly improved activity towards SAM. Molecular dynamic simulation revealed that these variants had more flexible loops, facilitating the release of SAM.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ryuichi Iwasaki, Tomohiro Bito, Atsushi Ishihara, Fumio Watanabe, Yukinori Yabuta
Summary: SAM and SAH are important biochemical intermediates, with SAM being the major methyl donor in vivo. The SAM to SAH ratio is a marker of methylation capacity. Stable isotope-labeled SAM and SAH are used to measure this ratio with high sensitivity. We focused on the SAHH of Pyrococcus horikoshii OT3 and prepared recombinant P. horikoshii SAHH to efficiently produce labeled SAH.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Zhong-Ce Hu, Chui-Mu Zheng, Yun-Chao Tao, Shu-Nan Wang, Yuan-Shan Wang, Zhi-Qiang Liu, Yu-Guo Zheng
Summary: This study aimed to increase the accumulation of S-adenosyl-L-methionine (SAM) in Saccharomyces cerevisiae by promoting ATP availability. The results showed that the lack of gene sod1 benefited ATP generation and positively regulated SAM synthesis. Additionally, improving substrate assimilation further enhanced SAM production. The SAM concentration of strain Delta SOD1 was increased from 7.3 g L-1 to 10.1 g L-1 in a 5-L fermenter.
ENZYME AND MICROBIAL TECHNOLOGY
(2023)
Review
Oncology
Jiamin Guo, Yanzhong Yang, Ralf Buettner, Steven T. Rosen
Summary: This review summarizes the biological roles of methionine, methionine adenosyl transferase 2A (MAT2A), and S-adenosyl methionine (SAM) in methylation reactions during tumorigenesis. It discusses newly emerged inhibitors targeting the methionine-MAT2A-SAM axis. Recent studies have confirmed the essential roles of methionine and MAT2A in SAM biosynthesis and validated MAT2A as a metabolic dependency of cancer cells. Inhibition of MAT2A has shown synthetic lethality in MTAP-deleted cancers. Notably, significant progress has been made in developing inhibitors targeting the methionine-MAT2A-SAM axis, with first-in-class MAT2A inhibitors entering clinical trials. The methionine-MAT2A-SAM axis plays a critical role in tumorigenesis through providing SAM for abnormal protein, DNA, and RNA methylation in cancer cells. Targeting SAM biosynthesis through MAT2A inhibition has emerged as a novel and promising strategy for cancer therapy.
CURRENT OPINION IN ONCOLOGY
(2022)
Article
Cell Biology
Yudong Sun, Jason W. Locasale
Summary: This article examines the chemical stability and cellular permeability of SAM, proposes a schematic for indirect transport of SAM across mammalian plasma membrane, and discusses the implications arising from such transport schematic.
Article
Biochemistry & Molecular Biology
Ian R. Price, Ahmed Gaballa, Fang Ding, John D. Helmann, Ailong Ke
Article
Biochemistry & Molecular Biology
Robert A. Battaglia, Ian R. Price, Ailong Ke
Article
Chemistry, Medicinal
Nicole A. Spiegelman, Jun Young Hong, Jing Hu, Hui Jing, Miao Wang, Ian R. Price, Ji Cao, Min Yang, Xiaoyu Zhang, Hening Lin
Article
Chemistry, Medicinal
Ali Sohail Farooqi, Jun Young Hong, Ji Cao, Xuan Lu, Ian Robert Price, Qingjie Zhao, Tatsiana Kosciuk, Min Yang, Jessica Jingyi Bai, Hening Lin
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Jun Young Hong, Ian Robert Price, Jessica Jingyi Bai, Hening Lie
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Rujie Cai, Ian R. Price, Fang Ding, Feifei Wu, Ting Chen, Yunlong Zhang, Guangfeng Liu, Paul J. Jardine, Changrui Lu, Ailong Ke
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Krishna C. Suddala, Ian R. Price, Shiba S. Dandpat, Michal Janecek, Petra Kuhrova, Jiri Sponer, Pavel Banas, Ailong Ke, Nils G. Walter
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Tatsiana Kosciuk, Ian R. Price, Xiaoyu Zhang, Chengliang Zhu, Kayla N. Johnson, Shuai Zhang, Steve L. Halaby, Garrison P. Komaniecki, Min Yang, Caroline J. DeHart, Paul M. Thomas, Neil L. Kelleher, J. Christopher Fromme, Hening Lin
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Medicinal
Jun Young Hong, Hui Jing, Ian Robert Price, Ji Cao, Jessica Jingyi Bai, Hening Lin
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Chemistry, Physical
Dan Su, Tatsiana Kosciuk, Min Yang, Ian R. Price, Hening Lin
Summary: Kinetic parameters are commonly used to characterize enzymes, but the substrate specificity of enzymes like NMT1 is actually determined by their binding affinity for different substrates rather than traditional kinetic values. Understanding this allows for the discovery of new substrate proteins through interactions with enzymes that catalyze post-translational modifications.
Article
Multidisciplinary Sciences
Shuai Zhang, Ornella D. Nelson, Ian R. Price, Chengliang Zhu, Xuan Lu, Irma R. Fernandez, Robert S. Weiss, Hening Lin
Summary: This study reveals that the metabolic intermediate LCFA-CoA regulates cancer metastasis by inhibiting NME1 and NME2, which play important roles in cellular protein functions such as clathrin-mediated endocytosis and cancer cell migration. The inhibitory effect of LCFA-CoA on NME1 compromises its metastasis suppressor function, especially under high-fat-diet conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Miao Wang, Yugang Zhang, Garrison P. Komaniecki, Xuan Lu, Ji Cao, Mingming Zhang, Tao Yu, Dan Hou, Nicole A. Spiegelman, Ming Yang, Ian R. Price, Hening Lin
Summary: This study reveals the role of protein deacetylase SIRT2 in Golgi stress induced by bacterial infection. Shigella secrete effector protein IcsB, which transfers fatty acyl groups to modify host proteins to evade immune surveillance. Upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Uzma Hameed, Ian Price, Ikram-Ul-Haq, Ailong Ke, David B. Wilson, Osman Mirza
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2017)
Article
Biochemistry & Molecular Biology
Damien Marchese, Florent Guislain, Tamara Pringels, Laure Bridoux
Summary: Homopolymeric amino acid repeats are common in human proteins, particularly in transcription factors and kinases. This study focuses on homopolymeric histidine repeats (polyH) and their role in regulating embryonic development. Through bioinformatic analysis, the study identifies that polyH-containing proteins interact with cysteine-rich proteins and proteins containing cysteine repeats. The study further investigates the HOXA1 protein, a transcription factor with a long polyH motif, and finds that the polyH motif is necessary for its interaction with cysteine-rich proteins. Additionally, the study discovers that metal ions are required for the HOXA1-MDFI interaction and identifies three polyH interactors that down-regulate the transcriptional activity of HOXA1.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2024)
