Review
Cell Biology
Zhanwu Hou, Huadong Liu
Summary: This paper discusses the central role of the kinome in cellular processes and disease development, and introduces the current strategies for kinome analysis. It also explores the development of tools for estimating spatial kinome activity.
Article
Biology
Haitao Zhang, Xiaolei Cao, Mei Tang, Guoxuan Zhong, Yuan Si, Haidong Li, Feifeng Zhu, Qinghua Liao, Liuju Li, Jianhui Zhao, Jia Feng, Shuaifeng Li, Chenliang Wang, Manuel Kaulich, Fangwei Wang, Liangyi Chen, Li Li, Zongping Xia, Tingbo Liang, Huasong Lu, Xin-Hua Feng, Bin Zhao
Summary: The human kinome consists of 538 kinases that play essential roles in catalyzing protein phosphorylation. The annotation and visualization of the subcellular distribution of these kinases in the Kinome Atlas (KA) provide insights into their functions and mechanisms, including new kinase localizations and the role of liquid-liquid phase separation in kinase condensate formation. Despite limitations such as potential mislocalization, the subcellular map of the kinome can be utilized to enhance our understanding of regulatory mechanisms involving protein phosphorylation.
Review
Pharmacology & Pharmacy
Deep Rohan Chatterjee, Saumya Kapoor, Meenakshi Jain, Rudradip Das, Moumita Ghosh Chowdhury, Amit Shard
Summary: The development of proteolysis-targeting chimeras (PROTACs) has led to the discovery of drugs that specifically target undruggable proteins. Small molecule-based PROTACs that target intracellular pathways have entered clinical trials, and their combination with antibodies has shown potent effects in cancer treatment. This review discusses the recent milestones and challenges in this area of drug development, as well as the best path forward.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Wayland Yeung, Annie Kwon, Rahil Taujale, Claire Bunn, Aarya Venkat, Natarajan Kannan
Summary: The emergence of multicellularity is closely linked to the expansion of tyrosine kinases, a family of signaling enzymes that regulate essential pathways for cell communication. This study identified ancient clades of cytoplasmic and receptor tyrosine kinases and described the presence of a fast-evolving insertion in nearly all receptor tyrosine kinases. The research also proposed the origin and evolution of the oldest tyrosine kinases and suggested that lineage-specific functionalities may be selectively altered in human cancers.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Multidisciplinary Sciences
Jared L. Johnson, Tomer M. Yaron, Emily M. Huntsman, Alexander Kerelsky, Junho Song, Amit Regev, Ting-Yu Lin, Katarina Liberatore, Daniel M. Cizin, Benjamin M. Cohen, Neil Vasan, Yilun Ma, Konstantin Krismer, Jaylissa Torres Robles, Bert van de Kooij, Anne E. van Vlimmeren, Nicole Andree-Busch, Norbert F. Kaeufer, Maxim Dorovkov, Alexey G. Ryazanov, Yuichiro Takagi, Edward R. Kastenhuber, Marcus D. Goncalves, Benjamin D. Hopkins, Olivier Elemento, Dylan J. Taatjes, Alexandre Maucuer, Akio Yamashita, Alexei Degterev, Mohamed Uduman, Jingyi Lu, Sean D. Landry, Bin Zhang, Ian Cossentino, Rune Linding, John Blenis, Peter Hornbeck, Benjamin E. Turk, Michael B. Yaffe, Lewis C. Cantley
Summary: Protein phosphorylation is a common post-translational modification, and thousands of phosphorylated sites have been associated with human diseases and biological processes. However, the responsible protein kinases for most phosphorylation events are currently unknown. This study used synthetic peptide libraries to profile the substrate specificity of 303 Ser/Thr kinases and identified the kinases capable of phosphorylating reported phosphorylation sites.
Article
Engineering, Civil
Jianmin Zhang, Ruichang Hu
Summary: Aquatic plants play a crucial role in altering flow patterns and sediment transport in rivers. This study examined the velocity and turbulence structures in a compound channel with varying riparian vegetation cover. The lateral profile of velocity can change to two distinct segments, the shear layer (SL) and the mixing layer (ML), influenced by bed morphology and vegetation. The lateral profile of Reynolds stress is bimodal, with the crest value decreasing as the ratio of nonvegetated floodplain width to bankfull height increases. Quasi-two-dimensional coherent structures were found in both the SL and ML, which greatly influenced Reynolds stress.
JOURNAL OF HYDROLOGY
(2023)
Article
Oncology
Sarah Ouahoud, Rutger J. Jacobs, Maikel P. Peppelenbosch, G. M. Fuhler, Jarom Heijmans, Sander Diks, Manon E. Wildenberg, Lucas J. A. C. Hawinkels, Liudmila L. Kodach, Philip W. Voorneveld, James C. H. Hardwick
Summary: This study reveals that statins induce BMP-specific activation of PTEN and inhibit PI3K/Akt/mTOR signaling in CRC. The effects of statins on cell signaling are specific and can be distinguished from nonspecific, toxic effects. Experiments in xenografts and in patients treated with Simvastatin confirm the activation of the BMP pathway, PTEN, and downregulation of mTOR signaling.
BRITISH JOURNAL OF CANCER
(2021)
Article
Chemistry, Medicinal
Dominique Sydow, Eva Assmann, Albert J. Kooistra, Friedrich Rippmann, Andrea Volkamer
Summary: Protein kinases are important drug targets, but developing selective inhibitors is challenging due to their structural conservation. This study presents a kinase fingerprint based on structural similarity that can predict off-targets. The fingerprint is a valuable tool in kinase research for guiding off-target and polypharmacology prediction.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Food Science & Technology
Hongkun Xue, Xiaohan Zhu, Jiaqi Tan, Linlin Fan, Qian Li, Jintian Tang, Xu Cai
Summary: An efficient strategy for selecting active compounds from blueberries was established using counter-current fractionation and bioassay-guided separation. The cyanidin-3-glucoside (C3G) was successfully separated with high purity, and its interaction mechanism with alpha-glucosidase was characterized through spectroscopic methods and molecular docking techniques. This study provides valuable insights for developing functional foods for type 2 diabetes management.
Article
Multidisciplinary Sciences
Bryan C. Jensen, Pashmi Vaney, John Flaspohler, Isabelle Coppens, Marilyn Parsons
Summary: In many eukaryotes, multiple protein kinases are located in the plasma membrane to respond to extracellular ligands, with signal transduction from the external environment to activate the cytosolic kinase domain. Humans have over 100 receptor protein kinases, while Trypanosoma brucei has only ten predicted transmembrane domain protein kinases, most of which are conserved in Trypanosoma cruzi and Leishmania species. These kinases are positioned in structures suggesting participation in signal transduction from the external environment.
Review
Biochemistry & Molecular Biology
Bingting Yu, Ruslan Mamedov, Gwenny M. Fuhler, Maikel P. Peppelenbosch
Summary: The liver plays a crucial role in maintaining biochemical balance, and diseases affecting the liver have a significant impact on human health. However, due to the complexity and uniqueness of hepatic kinase activities, there are challenges in studying them comprehensively. Nevertheless, current kinome profiling approaches show great promise for advancing research in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Marianna Krysinska, Bartosz Baranowski, Bartlomiej Deszcz, Krzysztof Pawlowski, Marcin Gradowski
Summary: In this study, using non-standard bioinformatic approaches, the researchers discovered 13 novel (pseudo)kinase families in the Legionella genus. They also analyzed the functional roles of these predicted kinases and found that some of them are present in other bacterial taxa, including other pathogens. This work highlights the ingenuity of nature in the pathogen-host arms race and provides a useful resource for the study of infection mechanisms.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Aziz M. Rangwala, Victoria R. Mingione, George Georghiou, Markus A. Seeliger
Summary: Phosphorylation plays a vital role in regulating biological processes, and protein kinases have been extensively studied for their involvement in human health and disease. Some kinases possess additional catalytic functions in addition to phosphotransferase activity, while others have lost their catalytic activity completely. In this study, we analyzed the UniProtKB database for bifunctional protein kinases and focused on those crucial for bacterial and human cellular homeostasis. These kinases have diverse functional roles in environmental sensing, metabolic regulation, immune-host defense, and cell cycle control. This article explores their dual catalytic activities and their contributions to disease pathogenesis.
Article
Multidisciplinary Sciences
Corvin Walter, Adinarayana Marada, Tamara Suhm, Ralf Ernsberger, Vera Muders, Cansu Kuecuekkoese, Pablo Sanchez-Martin, Zehan Hu, Abhishek Aich, Stefan Loroch, Fiorella Andrea Solari, Daniel Poveda-Huertes, Alexandra Schwierzok, Henrike Pommerening, Stanka Matic, Jan Brix, Albert Sickmann, Claudine Kraft, Joern Dengjel, Sven Dennerlein, Tilman Brummer, F. -Nora Voegtle, Chris Meisinger
Summary: The study shows that DYRK1A phosphorylates TOM70 to promote import of precursor proteins into mitochondria. Inhibition of DYRK1A impairs mitochondrial structure and function, leading to a decrease in metabolite carrier import capacity.
NATURE COMMUNICATIONS
(2021)
Article
Plant Sciences
Jose Ribamar Costa Ferreira-Neto, Artemisa Nazare da Costa Borges, Manasses Daniel da Silva, David Anderson de Lima Morais, Joao Pacifico Bezerra-Neto, Guillaume Bourque, Ederson Akio Kido, Ana Maria Benko-Iseppon
Summary: This pioneering study analyzed genomic and transcriptomic data from Vigna unguiculata (cowpea) kinases, providing insights into their structural characteristics, evolution, conservation among Viridiplantae species, and gene expression under different stress situations. The study revealed mechanisms of genomic expansion, conservation patterns, and up-regulation of specific families of kinases in response to stress, laying the foundation for further research on the evolution and molecular function of VuPKs.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Norbert Furtmann, Ye Hu, Michael Guetschow, Juergen Bajorath
CHEMICAL BIOLOGY & DRUG DESIGN
(2015)
Article
Chemistry, Multidisciplinary
Norbert Furtmann, Daniela Haeussler, Tamara Scheidt, Marit Stirnberg, Torsten Steinmetzer, Juergen Bajorath, Michael Guetschow
CHEMISTRY-A EUROPEAN JOURNAL
(2016)
Article
Chemistry, Medicinal
Janina Schmitz, Norbert Furtmann, Moritz Ponert, Maxim Frizler, Reik Loeser, Ulrike Bartz, Juergen Bajorath, Michael Guetschow
Review
Chemistry, Medicinal
Norbert Furtmann, Juergen Bajorath
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Organic
Franziska Kohl, Janina Schmitz, Norbert Furtmann, Anna-Christina Schulz-Fincke, Matthias D. Mertens, Jim Kueppers, Marcel Benkhoff, Edda Tobiasch, Ulrike Bartz, Jurgen Bajorath, Marit Stirnberg, Michael Guetschow
ORGANIC & BIOMOLECULAR CHEMISTRY
(2015)
Article
Chemistry, Organic
Norbert Furtmann, Erik Gilberg, Nicola Spuetz, Michael Guetschow
SYNTHESIS-STUTTGART
(2015)
Article
Chemistry, Multidisciplinary
Norbert Furtmann, Ye Hu, Michael Guetschow, Juergen Bajorath
Article
Biochemistry & Molecular Biology
Aliya Ibrar, Yildiz Tehseen, Imtiaz Khan, Abdul Hameed, Aamer Saeed, Norbert Furtmann, Juergen Bajorath, Jamshed Iqbal
BIOORGANIC CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Anna-Madeleine Beckmann, Eva Maurer, Verena Luelsdorff, Annika Wilms, Norbert Furtmann, Juergen Bajorath, Michael Guetschow, Marit Stirnberg
Article
Chemistry, Multidisciplinary
Daniela Haeussler, Martin Mangold, Norbert Furtmann, Annett Braune, Michael Blaut, Juergen Bajorath, Marit Stirnberg, Michael Guetschow
CHEMISTRY-A EUROPEAN JOURNAL
(2016)
Article
Microbiology
Annett Braune, Wolfram Engst, Paul W. Elsinghorst, Norbert Furtmann, Juergen Bajorath, Michael Guetschow, Michael Blaut
JOURNAL OF BACTERIOLOGY
(2016)
Article
Chemistry, Medicinal
Norbert Furtmann, Ye Hu, Juergen Bajorath
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Wanwisa Promsote, Ling Xu, Jason Hataye, Giulia Fabozzi, Kylie March, Cassandra G. Almasri, Megan E. DeMouth, Sarah E. Lovelace, Chloe Adrienna Talana, Nicole A. Doria-Rose, Krisha McKee, Sabrina Helmold Hait, Joseph P. Casazza, David Ambrozak, Jochen Beninga, Ercole Rao, Norbert Furtmann, Joerg Birkenfeld, Elizabeth McCarthy, John-Paul Todd, Constantinos Petrovas, Mark Connors, Andrew T. Hebert, Jeremy Beck, Junqing Shen, Bailin Zhang, Mikhail Levit, Ronnie R. Wei, Zhi-yong Yang, Amarendra Pegu, John R. Mascola, Gary J. Nabel, Richard A. Koup
Summary: Researchers have developed a trispecific antibody that can activate and target latently HIV-1 infected cells for elimination by T cells, providing an alternative strategy for curing HIV.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Ye Hu, Norbert Furtmann, Juergen Bajorath