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SARS-CoV-2 Mpro inhibitors and activity-based probes for patient-sample imaging.

Wioletta Rut, Katarzyna Groborz, Linlin Zhang, Xinyuanyuan Sun, Mikolaj Zmudzinski, Bartlomiej Pawlik, Xinyu Wang, Dirk Jochmans, Johan Neyts, Wojciech Młynarski, Rolf Hilgenfeld, Marcin Drag,

In December 2019, the first cases of infection with a novel coronavirus, SARS-CoV-2, were diagnosed. Currently, there is no effective antiviral treatment for COVID-19. To address this emerging problem, we focused on the SARS-CoV-2 main protease that constitutes one of the most attractive antiviral drug targets. We have synthesized a ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2.

Colton J Bracken, Shion A Lim, Paige Solomon, Nicholas J Rettko, Duy P Nguyen, Beth Shoshana Zha, Kaitlin Schaefer, James R Byrnes, Jie Zhou, Irene Lui, Jia Liu, Katarina Pance, , Xin X Zhou, Kevin K Leung, James A Wells,

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 ... Read more >>

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[2020, :]

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Cuticle thickness affects dynamics of volatile emission from petunia flowers.

Pan Liao, Shaunak Ray, Benoît Boachon, Joseph H Lynch, Arnav Deshpande, Scott McAdam, John A Morgan, Natalia Dudareva,

The plant cuticle is the final barrier for volatile organic compounds (VOCs) to cross for release to the atmosphere, yet its role in the emission process is poorly understood. Here, using a combination of reverse-genetic and chemical approaches, we demonstrate that the cuticle imposes substantial resistance to VOC mass transfer, ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Reversal of nucleobase methylation by dioxygenases.

Guo-Liang Xu, Matthias Bochtler,

The repertoire of nucleobase methylation in DNA and RNA, introduced by chemical agents or enzymes, is large. Most methylation can be reversed either directly by restoration of the original nucleobase or indirectly by replacement of the methylated nucleobase with an unmodified nucleobase. In many direct and indirect demethylation reactions, ALKBH ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, 16(11):1160-1169]

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Peroxisome compartmentalization of a toxic enzyme improves alkaloid production.

Parbir S Grewal, Jennifer A Samson, Jordan J Baker, Brian Choi, John E Dueber,

Eukaryotic cells compartmentalize metabolic pathways in organelles to achieve optimal reaction conditions and avoid crosstalk with cytosolic factors. We found that cytosolic expression of norcoclaurine synthase (NCS), the enzyme that catalyzes the first committed reaction in benzylisoquinoline alkaloid biosynthesis, is toxic in Saccharomyces cerevisiae and, consequently, restricts (S)-reticuline production. We ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Discovery of iron-sensing bacterial riboswitches.

Siladitya Bandyopadhyay, Susmitnarayan Chaudhury, Dolly Mehta, Arati Ramesh,

Despite the central role of iron in biology, our understanding of how cells sense iron is limited to protein-dependent mechanisms. Here, we report the discovery of iron-sensing riboswitches (named Sensei). Present across bacterial phyla, these RNAs reside in the 5' untranslated regions or within coding regions of messenger RNAs (mRNAs) ... Read more >>

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[2020, :]

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Sulfated glycans engage the Ang-Tie pathway to regulate vascular development.

Matthew E Griffin, Alexander W Sorum, Gregory M Miller, William A Goddard, Linda C Hsieh-Wilson,

The angiopoietin (Ang)-Tie pathway is essential for the proper maturation and remodeling of the vasculature. Despite its importance in disease, the mechanisms that control signal transduction through this pathway are poorly understood. Here, we demonstrate that heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang-Tie signaling through direct interactions with both Ang ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Shifting the balance.

Grant Miura,

Nat. Chem. Biol. (Nature chemical biology)
[2020, 16(10):1037]

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Toward spatially resolved metabolomics.

Bennett W Fox, Frank C Schroeder,

Nat. Chem. Biol. (Nature chemical biology)
[2020, 16(10):1039-1040]

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Importin pain relief.

Mirella Bucci,

Nat. Chem. Biol. (Nature chemical biology)
[2020, 16(10):1037]

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PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase.

Bikash Adhikari, Jelena Bozilovic, Mathias Diebold, Jessica Denise Schwarz, Julia Hofstetter, Martin Schröder, Marek Wanior, Ashwin Narain, Markus Vogt, Nevenka Dudvarski Stankovic, Apoorva Baluapuri, Lars Schönemann, Lorenz Eing, Pranjali Bhandare, Bernhard Kuster, Andreas Schlosser, Stephanie Heinzlmeir, Christoph Sotriffer, Stefan Knapp, Elmar Wolf,

The mitotic kinase AURORA-A is essential for cell cycle progression and is considered a priority cancer target. Although the catalytic activity of AURORA-A is essential for its mitotic function, recent reports indicate an additional non-catalytic function, which is difficult to target by conventional small molecules. We therefore developed a series ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, 16(11):1179-1188]

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CueR activates transcription through a DNA distortion mechanism.

Chengli Fang, Steven J Philips, Xiaoxian Wu, Kui Chen, Jing Shi, Liqiang Shen, Juncao Xu, Yu Feng, Thomas V O'Halloran, Yu Zhang,

The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshaping promoter DNA. To address the question ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Made fresh in-house.

Yiyun Song,

Nat. Chem. Biol. (Nature chemical biology)
[2020, 16(10):1037]

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Three's company.

Caitlin Deane,

Nat. Chem. Biol. (Nature chemical biology)
[2020, 16(10):1037]

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Uncovering nature's electronics.

Thomas A Clarke, Marcus J Edwards,

Nat. Chem. Biol. (Nature chemical biology)
[2020, 16(10):1041-1042]

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Publisher Correction: A mass spectrometry-based proteome map of drug action in lung cancer cell lines.

Benjamin Ruprecht, Julie Di Bernardo, Zhao Wang, Xuan Mo, Oleg Ursu, Matthew Christopher, Rafael B Fernandez, Li Zheng, Brian D Dill, Huijun Wang, Yuting Xu, Andy Liaw, Jonathan D Mortison, Nirodhini Siriwardana, Brian Andresen, Meir Glick, James R Tata, Victoria Kutilek, Ivan Cornella-Taracido, An Chi,

An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, 16(10):1149]

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A stress-free stress response.

Nadia Cummins, Rebecca C Taylor,

Nat Chem Biol (Nature chemical biology)
[2020, 16(10):1038-1039]

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Designer adhesion GPCR tells its signaling story.

Eugenia V Gurevich, Vsevolod V Gurevich,

Nat. Chem. Biol. (Nature chemical biology)
[2020, :]

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An ultrasensitive biosensor for high-resolution kinase activity imaging in awake mice.

Jin-Fan Zhang, Bian Liu, Ingie Hong, Albert Mo, Richard H Roth, Brian Tenner, Wei Lin, Jason Z Zhang, Rosana S Molina, Mikhail Drobizhev, Thomas E Hughes, Lin Tian, Richard L Huganir, Sohum Mehta, Jin Zhang,

Protein kinases control nearly every facet of cellular function. These key signaling nodes integrate diverse pathway inputs to regulate complex physiological processes, and aberrant kinase signaling is linked to numerous pathologies. While fluorescent protein-based biosensors have revolutionized the study of kinase signaling by allowing direct, spatiotemporally precise kinase activity measurements ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Glucosylation prevents plant defense activation in phloem-feeding insects.

Osnat Malka, Michael L A E Easson, Christian Paetz, Monika Götz, Michael Reichelt, Beate Stein, Katrin Luck, Aleksa Stanišić, Ksenia Juravel, Diego Santos-Garcia, Lilach L Mondaca, Simon Springate, John Colvin, Stephan Winter, Jonathan Gershenzon, Shai Morin, Daniel G Vassão,

The metabolic adaptations by which phloem-feeding insects counteract plant defense compounds are poorly known. Two-component plant defenses, such as glucosinolates, consist of a glucosylated protoxin that is activated by a glycoside hydrolase upon plant damage. Phloem-feeding herbivores are not generally believed to be negatively impacted by two-component defenses due to ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Selective regulation of human TRAAK channels by biologically active phospholipids.

Samantha Schrecke, Yun Zhu, Jacob W McCabe, Mariah Bartz, Charles Packianathan, Minglei Zhao, Ming Zhou, David Russell, Arthur Laganowsky,

TRAAK is an ion channel from the two-pore domain potassium (K2P) channel family with roles in maintaining the resting membrane potential and fast action potential conduction. Regulated by a wide range of physical and chemical stimuli, the affinity and selectivity of K2P4.1 toward lipids remains poorly understood. Here we show ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Organelle membrane-specific chemical labeling and dynamic imaging in living cells.

Tomonori Tamura, Alma Fujisawa, Masaki Tsuchiya, Yuying Shen, Kohjiro Nagao, Shin Kawano, Yasushi Tamura, Toshiya Endo, Masato Umeda, Itaru Hamachi,

Lipids play crucial roles as structural elements, signaling molecules and material transporters in cells. However, the functions and dynamics of lipids within cells remain unclear because of a lack of methods to selectively label lipids in specific organelles and trace their movement by live-cell imaging. We describe here a technology ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells.

Junichi Yamamoto, Tetsufumi Suwa, Yuki Murase, Shumpei Tateno, Hirotaka Mizutome, Tomoko Asatsuma-Okumura, Nobuyuki Shimizu, Tsutomu Kishi, Shuji Momose, Masahiro Kizaki, Takumi Ito, Yuki Yamaguchi, Hiroshi Handa,

The immunomodulatory drug (IMiD) thalidomide and its derivatives lenalidomide and pomalidomide are therapeutic agents used in the treatment of multiple myeloma. Although pomalidomide offers considerable clinical benefits to patients with lenalidomide-resistant multiple myeloma, the molecular mechanisms underlying its superior efficacy remain unclear. Here we show that ARID2, a component of ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, 16(11):1208-1217]

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Bacterial virulence mediated by orthogonal post-translational modification.

Kaitlin A Chambers, Rebecca A Scheck,

Many bacterial pathogens secrete virulence factors, also known as effector proteins, directly into host cells. These effectors suppress pro-inflammatory host signaling while promoting bacterial infection. A particularly interesting subset of effectors post-translationally modify host proteins using novel chemistry that is not otherwise found in the mammalian proteome, which we refer ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, 16(10):1043-1051]

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Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling.

Xiaofeng Qi, Lucas Friedberg, Ryan De Bose-Boyd, Tao Long, Xiaochun Li,

Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain (CRD) and to several sites in the seven transmembrane helices (7-TMs) of SMO. However, the mechanism by which sterols regulate SMO via multiple sites ... Read more >>

Nat. Chem. Biol. (Nature chemical biology)
[2020, :]

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