Article
Chemistry, Medicinal
Oliver Laufkoetter, Huabin Hu, Filip Miljkovic, Juergen Bajorath
Summary: Allosteric kinase inhibitors are highly selective and promising candidates for kinase drug discovery. Exploring allosteric mechanisms is of great interest in basic research and drug design. X-ray structures of kinase complexes have provided valuable data for identifying and characterizing allosteric inhibitors. This study presents a comprehensive survey of allosteric kinase inhibitors and activators based on publicly available X-ray structures, mapping their binding sites and distribution in kinase binding pockets. The structural features of these compounds are discussed, and active structural analogues and high-confidence target annotations are identified, suggesting additional activities for some allosteric inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tao Huang, Seyyedmohsen Hosseinibarkooie, Adam L. Borne, Mitchell E. Granade, Jeffrey W. Brulet, Thurl E. Harris, Heather A. Ferris, Ku-Lung Hsu
Summary: The sulfonyl-triazoles (SuTEx) chemistry is a new type of electrophile that can react covalently with proteins, useful for chemical proteomics and protein ligand discovery. Functionalized SuTEx probes have been utilized to map protein interaction networks and discover binding sites in live cells, leading to the identification of important probe-modified sites within the protein kinase C-alpha C2 domain.
Article
Biotechnology & Applied Microbiology
Subhankar Biswas, Raju Mondal, Akanksha Srivastava, Maitri Trivedi, Sunil Kumar Singh, Yogesh Mishra
Summary: The study investigated the role of legume lectin-like proteins (LLPs) in Arabidopsis thaliana under various abiotic stresses. Analysis of AtLLPs' chromosomal localization, gene structure, protein motif, peptide sequence, phylogeny, and sub-cellular localization was conducted, revealing different expression patterns in response to abiotic stresses. The presence of important cis-regulatory elements (CREs) in the promoter sequences of AtLLPs suggested their involvement in regulating abiotic stress responses, supported by the expressional correlation analysis with CREs cognate transcription factors (TFs).
Review
Biochemistry & Molecular Biology
Haofan Zhang, Fengming He, Guiping Gao, Sheng Lu, Qiaochu Wei, Hongyu Hu, Zhen Wu, Meijuan Fang, Xiumin Wang
Summary: Kinases are crucial in regulating cell processes like proliferation, apoptosis, and metabolism, and their dysregulation and mutation are linked to various diseases, particularly cancer. As a result, numerous small-molecule drugs targeting kinases have been developed and approved for disease treatment. The indole/azaindole/oxindole moiety is an important pharmacophore and scaffold in medicinal chemistry, with 30 ATP-competitive kinase inhibitors based on this scaffold already approved. This article summarizes the research and development process of these inhibitors, their binding models to ATP-binding sites, and discusses the significance of the indole/azaindole/oxindole structure in interactions between the inhibitors and target kinases, providing inspiration for future kinase inhibitor development.
Article
Cell Biology
Kaiming Cao, Shixuan Li, Yu Wang, Hongze Hu, Sijia Xiang, Qianling Zhang, Yangzhong Liu
Summary: Recently, it has been discovered that bacterial cells contain membrane-less organelles formed by liquid-liquid phase separation of proteins or nucleic acids. In this study, it was found that the bacterial nickel-responsive regulatory protein, NikR, exhibits liquid-liquid phase separation in both solution and cells. Furthermore, disrupting the phase separation promotes the expression of nickel transporter genes, suggesting that the formation of these membrane-less compartments is a regulatory mechanism in bacterial cells.
Article
Chemistry, Multidisciplinary
Isabel V. L. Wilkinson, Max Bottlinger, Yassmine El Harraoui, Stephan A. Sieber
Summary: Heme is a cofactor that plays myriad roles and is essential to almost all living organisms. It is now recognized as a tightly controlled signaling molecule that regulates protein expression. However, our understanding of heme acquisition, biosynthesis, and regulation is limited, especially in bacteria. In this study, a chemical proteomics method was developed to profile heme-binding proteins in live cells for the first time. This strategy successfully identified a significant portion of the heme-binding proteome in Gram-positive and Gram-negative bacteria and has the potential to fuel future research in heme biology.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Marrit M. E. Tholen, Roderick P. Tas, Yuyang Wang, Lorenzo Albertazzi
Summary: In the last decade, point accumulation for imaging in nanoscale topography (PAINT) has become a versatile tool for single-molecule localization microscopy (SMLM). Currently, DNA-PAINT is widely used to reconstruct specific characteristics of biological or synthetic materials on a single-molecule level. However, there is a growing demand for PAINT probes that do not depend on DNA. These probes can be based on various interactions and provide complementary applications for SMLM. Researchers have been expanding the PAINT toolbox with new probes that go beyond DNA, which are discussed in this review.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Multidisciplinary
Benjamin Emenike, Ogonna Nwajiobi, Monika Raj
Summary: Nature increases the functional diversity of the proteome through posttranslational modifications (PTMs), which can be correlated to diseases. Therefore, it is important to qualitatively and quantitatively detect these transformations. One effective method is to use chemical strategies to label different PTMs, facilitating the study of their roles.
FRONTIERS IN CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Zikun Zhu, Shuai Wang, Shu-ou Shan
Summary: Using ribosome profiling methods, this study elucidates the cotranslational interaction principles of SecA with nascent proteins and reveals a hierarchical organization of protein export pathways in bacteria.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kyung Woo Kim, Sentaro Kusuhara, Atsuko Katsuyama-Yoshikawa, Sho Nobuyoshi, Megumi Kitamura, Sotaro Mori, Noriyuki Sotani, Kaori Ueda, Wataru Matsumiya, Akiko Miki, Takuji Kurimoto, Hisanori Imai, Makoto Nakamura
Summary: The study aimed to investigate the combined effects of aging and MRP4 deficiency on mouse retinas using gene expression microarray, morphological, and electrophysiological analyses. Results showed significant differences in gene expression in the retinas of aged Mrp4-null mice compared to aged WT mice, but no significant changes were observed in retinal thickness, morphology, or distribution of cells among different age/genotype groups. The electroretinogram responses also did not show significant differences between aged WT mice and aged Mrp4-null mice.
Article
Pharmacology & Pharmacy
Hiroki Hashizume, Tatsuki Fukami, Kanji Mishima, Hiroshi Arakawa, Kenji Mishiro, Yongjie Zhang, Masataka Nakano, Miki Nakajima
Summary: This study aimed to clarify the human ACS isoforms responsible for CoA-conjugation of NSAIDs by considering the hepatic expression levels of ACS isoforms. Among the 10 types of NSAIDs studied, propionic acid-class NSAIDs were found to be conjugated with CoA in the human liver, while NSAIDs in other classes did not exhibit this reaction. ACSL1 was identified as the most highly expressed ACS isoform in the human liver, and could catalyze the CoA conjugation of propionic acid-class NSAIDs, which may lead to toxicity through protein adduct formation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biology
Zhangqing Wang, Yanting Zhang, Yisong Liu, Dali Fu, Zhang You, Panpan Huang, Huiling Gao, Zhenqian Zhang, Cun Wang
Summary: Iron (Fe) is essential for all organisms, but its availability in the soil is often insufficient for plant growth, leading to iron deficiencies that affect crop yield. This study investigates the role of calcium (Ca2+) in regulating iron deficiency and identifies two calcium-dependent protein kinases (CPK21 and CPK23) that play a critical role in plant tolerance to iron-deficient conditions. The study also reveals the interaction and phosphorylation of the iron transporter IRT1 by CPK21 and CPK23, and identifies a critical residue (Ser149) for IRT1 transport activity.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Review
Plant Sciences
Gara Romero-Hernandez, Manuel Martinez
Summary: The success of plant response to environmental stressors depends on regulatory networks and phosphorylation plays a key role in activating or deactivating proteins. Protein kinases are responsible for phosphorylation and play an important role in signal transmission. This review focuses on the contribution of protein kinases to herbivore-triggered responses in plants.
FRONTIERS IN PLANT SCIENCE
(2022)
Editorial Material
Plant Sciences
Vishal Varshney, Abhijit Hazra, Manoj Majee
Summary: The process of seed germination is influenced by environmental cues, such as light, through photosensory systems and phytochromes. While this pathway has been known for a long time, the molecular mechanisms underlying it are still not fully understood. Li et al. recently demonstrated the role of ETHYLENE RESPONSE FACTORs (ERFs) in modulating phytochrome-mediated regulation of germination.
TRENDS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Deepti Sharan, Erin E. Carlson
Summary: In this study, the PBP inhibition profiles of 16 commercially available beta-lactam antibiotics were evaluated in an unencapsulated derivative of Streptococcus pneumoniae. The results showed that most of these antibiotics were co-selective for PBP2x and PBP3, with one molecule being co-selective for PBP1a and PBP3. This work expands the chemical space for the development of beta-lactam-based probes for specific pneumococcal PBP labeling and can also be applied to other bacterial species.
BIOLOGICAL CHEMISTRY
(2022)
Review
Plant Sciences
Alice Godson, Renier A. L. van der Hoorn
Summary: Apoplastic proteases play crucial roles in plant defense, with most being induced upon infection and 17 genetically required for the immune response. While the proteolytic activity of these proteases has been confirmed, its necessity for biological function is not always clear.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Plant Sciences
Lennard van der Woude, Markus Piotrowski, Gruson Klaasse, Judith K. Paulus, Daniel Krahn, Sabrina Ninck, Farnusch Kaschani, Markus Kaiser, Ondrej Novak, Karin Ljung, Suzanne Bulder, Marcel van Verk, Basten L. Snoek, Martijn Fiers, Nathaniel I. Martin, Renier A. L. van Der Hoorn, Stephanie Robert, Sjef Smeekens, Martijn van Zanten
Summary: The study identified a small molecule compound named 'Heatin' that enhances hypocotyl elongation in Arabidopsis under warm temperature conditions by inhibiting the enzymatic activity of the NITRILASE1-subfamily and promoting the synthesis of bioactive auxin. This finding provides a novel chemical entity for studying auxin biology and suggests a potential indirect mechanism through which nitrilases contribute to the Heatin response.
Article
Plant Sciences
Kyoko Morimoto, Daniel Krahn, Farnusch Kaschani, Digby Hopkinson-Woolley, Anna Gee, Pierre Buscaill, Shabaz Mohammed, Stephan A. Sieber, Benjamin F. Cravatt, Christopher J. Schofield, Renier A. L. van der Hoorn
Summary: This study introduces the use of hydroxamate-based photoaffinity probes to study plant metalloproteases. The probes were able to detect and identify different metalloprotease families in various subcellular compartments, revealing their role in auxin release and immune response.
Article
Multidisciplinary Sciences
Heike Chauvistre, Batool Shannan, Sheena M. Daignault-Mill, Robert J. Ju, Daniel Picard, Stefanie Egetemaier, Renata Varaljai, Christine S. Gibhardt, Antonio Sechi, Farnusch Kaschani, Oliver Keminer, Samantha J. Stehbens, Qin Liu, Xiangfan Yin, Kirujan Jeyakumar, Felix C. E. Vogel, Clemens Krepler, Vito W. Rebecca, Linda Kubat, Smiths S. Lueong, Jan Forster, Susanne Horn, Marc Remke, Michael Ehrmann, Annette Paschen, Juergen C. Becker, Iris Helfrich, Daniel Rauh, Markus Kaiser, Sheraz Gul, Meenhard Herlyn, Ivan Bogeski, Jose Neptuno Rodriguez-Lopez, Nikolas K. Haass, Dirk Schadendorf, Alexander Roesch
Summary: This study demonstrates that maintaining a high expression of KDM5B in slow-cycling melanoma cells can induce their differentiation and cell cycle arrest, thereby limiting tumor plasticity. The study also identifies a chemical agent, Cpd1, that can phenocopy the effect of high KDM5B expression and sensitizes melanoma cells to a specific antifolate prodrug.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Christian Schmerling, Leonard Sewald, Geronimo Heilmann, Frederick Witfeld, Dominik Begerow, Kenneth Jensen, Christopher Braesen, Farnusch Kaschani, Herman S. Overkleeft, Bettina Siebers, Markus Kaiser
Summary: Activity-based protein profiling is an effective method for screening enzymes with specific activity, and this study demonstrates its potential in discovering lignocellulose-degrading enzymes. It provides a preselection procedure for identifying promising biocatalysts and allows functional annotation of unknown domains.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Biology
Christian Schmerling, Leonard Sewald, Geronimo Heilmann, Frederick Witfeld, Dominik Begerow, Kenneth Jensen, Christopher Braesen, Farnusch Kaschani, Herman S. Overkleeft, Bettina Siebers, Markus Kaiser
COMMUNICATIONS BIOLOGY
(2022)
Article
Plant Sciences
Daniela J. Sueldo, Alice Godson, Farnusch Kaschani, Daniel Krahn, Till Kessenbrock, Pierre Buscaill, Christopher J. Schofield, Markus Kaiser, Renier A. L. van Der Hoorn
Summary: This study reports the dynamics of extracellular hydrolases in Nicotiana benthamiana upon infection with Pseudomonas syringae. The activity of 82 hydrolases, mostly serine hydrolases, increases during infection, while the activity of 60 hydrolases, mostly glycosidases and cysteine proteases, is suppressed. The study also reveals the antibacterial activity of NbPR3 and its essential active site substitution.
Letter
Plant Sciences
Rawit Longsaward, Nattapong Sanguankiattichai, Unchera Viboonjun, Renier A. L. van der Hoorn
PLANT AND CELL PHYSIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Isobel Dodds, Changlong Chen, Pierre Buscaill, Renier A. L. van Der Hoorn
Summary: Nicotiana benthamiana is increasingly used for transient gene expression but the expression is low in fully developed plants. The perception of cold shock protein (CSP) is thought to be the cause. This study demonstrates that silencing NbCORE in older plants increases GFP fluorescence and protein production, allowing for more efficient protein expression.
PLANT BIOTECHNOLOGY JOURNAL
(2023)
Article
Multidisciplinary Sciences
Mike Blueggel, Alexander Kroening, Matthias Kracht, Johannes van den Boom, Matthias Dabisch, Anna Goehring, Farnusch Kaschani, Markus Kaiser, Peter Bayer, Hemmo Meyer, Christine Beuck
Summary: This study investigates the biochemical function and structural organization of UBXD1 on p97. An extended UBX module in UBXD1 related to another cofactor, ASPL, is identified. The UBXD1-eUBX module intramolecularly associates with the PUB domain in UBXD1 close to the substrate exit pore of p97. Additionally, UBXD1 can bind the proteasomal shuttling factor HR23b and has ubiquitin binding activity. The findings suggest that the UBXD1-eUBX module plays an important role in the unfoldment of ubiquitinated substrates.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Maria Barco-Antonanzas, Maria Font-Farre, Mikel V. Eceiza, Miriam Gil-Monreal, Renier A. L. van der Hoorn, Mercedes Royuela, Ana Zabalza
Summary: This study demonstrates that glyphosate and pyrithiobac have significant inhibitory effects on EPSPS and ALS enzymes. The protease activity profiles of different populations of Amaranthus palmeri in response to these herbicides were characterized. The results show that both herbicides induce increased cysteine protease activity and amino acid accumulation, indicating their role in protein degradation and increased free amino acids. Conversely, no changes in proteolytic activities were observed in populations with target-site resistance, suggesting this effect is specific to sensitive plants.
PHYSIOLOGIA PLANTARUM
(2023)
Article
Plant Sciences
Maria Font Farre, Daniel Brown, Maurice Konig, Brian J. Killinger, Farnusch Kaschani, Markus Kaiser, Aaron T. Wright, Jonathan Burton, Renier A. L. van der Hoorn
Summary: This study presents an easy and quick assay for photoaffinity labeling of GSTs in different plant species. The results demonstrate that GSTs can be induced by various types of stress and this method is useful for studying GST induction in different plant species.
PLANT AND CELL PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Felix Homma, Jie Huang, Renier A. L. van der Hoorn
Summary: This study used AlphaFold-Multimer to screen small secreted proteins (SSPs) from plant pathogens and identified non-annotated SSPs that interact with tomato defense enzymes. Four of these SSPs were confirmed as inhibitors of subtilase P69B, demonstrating the application of AI in predicting cross-kingdom protein interactions.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Maximilian Ruettermann, Michelle Koci, Pascal Lill, Ermis Dionysios Geladas, Farnusch Kaschani, Bjoern Udo Klink, Ralf Erdmann, Christos Gatsogiannis
Summary: This study provides cryo-EM structures of Pex1/Pex6 and reveals their mechanism of protein substrate translocation. Pex1/Pex6 generates mechanical forces through ATP hydrolysis to drive substrate transport across the peroxisomal membrane.
NATURE COMMUNICATIONS
(2023)