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The first step of hypusination Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-30 Sophie McKenna
Hypusination is a two-step enzyme-mediated post-translational modification that converts lysine into hypusine. The modification is unique to the eukaryotic translation factor eIF5A, which is essential for overcoming ribosome stalling in polyproline regions. Dysregulation of hypusination is implicated in cancer, diabetes and hypusination-related neurodegeneration, including the recently identified neurodevelopmental
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Toxin-targeted transport Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-30 Russell Johnson
Cell-type-specific delivery of therapeutics requires selectivity to prevent delivery to off-target cells. However, developing methods that provide the desired selectivity remains challenging. Toxins such as anthrax, botulinum and diphtheria toxin have been explored as delivery systems due to their ability to undergo endocytosis through interactions with cells via the toxin receptor-binding domain and
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Seismic shift Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-30 Grant Miura
Original reference: Mol. Cell 83, 1725–1742.e12 (2023)
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Accelerating enzyme evolution Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-30 Russell Johnson
Enzymes have many highly desirable properties as catalysts, but adapting them to non-natural reactions or conditions requires re-design and optimization. One approach is directed evolution, which does not require prior knowledge of the structure or enzyme dynamics but takes many rounds to generate catalysts with the desired attributes or reactivity. Continuous evolution of enzymes in a high-throughput
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Superbugs leave fingerprints Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-30 Majda Bratovič
Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known superbug that has the staphylococcal cassette chromosome mec, a mobile genetic element containing genes that enable resistance to β-lactam antibiotics. Specifically, the mecA gene encodes the penicillin-binding protein PBP2a involved in peptidoglycan biosynthesis, cell-wall formation and resistance to antibiotics. MRSA can be categorized
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Microbiota metabolites as agonists for the orphan receptor GPRC5A Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-29
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Spontaneously established syntrophic yeast communities improve bioproduction Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-29 Simran Kaur Aulakh, Lara Sellés Vidal, Eric J. South, Huadong Peng, Sreejith Jayasree Varma, Lucia Herrera-Dominguez, Markus Ralser, Rodrigo Ledesma-Amaro
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Chemoproteomics reveals microbiota-derived aromatic monoamine agonists for GPRC5A Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-29 Xiaohui Zhao, Kathryn R. Stein, Victor Chen, Matthew E. Griffin, Luke L. Lairson, Howard C. Hang
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Nucleophilic covalent ligand discovery for the cysteine redoxome Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-29 Ling Fu, Youngeun Jung, Caiping Tian, Renan B. Ferreira, Ruifeng Cheng, Fuchu He, Jing Yang, Kate S. Carroll
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Nonmonotone invasion landscape by noise-aware control of metastasis activator levels Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-25 Yiming Wan, Joseph Cohen, Mariola Szenk, Kevin S. Farquhar, Damiano Coraci, Rafał Krzysztoń, Joshua Azukas, Nicholas Van Nest, Alex Smashnov, Yi-Jye Chern, Daniela De Martino, Long Chi Nguyen, Harold Bien, Jose Javier Bravo-Cordero, Chia-Hsin Chan, Marsha Rich Rosner, Gábor Balázsi
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Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-25 Gary Liu, Denise B. Catacutan, Khushi Rathod, Kyle Swanson, Wengong Jin, Jody C. Mohammed, Anush Chiappino-Pepe, Saad A. Syed, Meghan Fragis, Kenneth Rachwalski, Jakob Magolan, Michael G. Surette, Brian K. Coombes, Tommi Jaakkola, Regina Barzilay, James J. Collins, Jonathan M. Stokes
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Structural basis for Lewis antigen synthesis by the α1,3-fucosyltransferase FUT9 Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-18 Renuka Kadirvelraj, Bhargavi M. Boruah, Shuo Wang, Digantkumar Chapla, Chin Huang, Annapoorani Ramiah, Kieran L. Hudson, Anthony R. Prudden, Geert-Jan Boons, Stephen G. Withers, Zachary A. Wood, Kelley W. Moremen
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In-cell protein stability promotes antimicrobial resistance of metallo-β-lactamases Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-15
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Single-cell multi-omics in the medicinal plant Catharanthus roseus Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-15 Chenxin Li, Joshua C. Wood, Anh Hai Vu, John P. Hamilton, Carlos Eduardo Rodriguez Lopez, Richard M. E. Payne, Delia Ayled Serna Guerrero, Klaus Gase, Kotaro Yamamoto, Brieanne Vaillancourt, Lorenzo Caputi, Sarah E. O’Connor, C. Robin Buell
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In-cell kinetic stability is an essential trait in metallo-β-lactamase evolution Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-15 Lisandro J. González, Guillermo Bahr, Mariano M. González, Robert A. Bonomo, Alejandro J. Vila
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A platform for distributed production of synthetic nitrated proteins in live bacteria Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-15 Neil D. Butler, Sabyasachi Sen, Lucas B. Brown, Minwei Lin, Aditya M. Kunjapur
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Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-11 Yue Wang, Weiyi Liu, Youwei Xu, Xinheng He, Qingning Yuan, Ping Luo, Wenjia Fan, Jingpeng Zhu, Xinyue Zhang, Xi Cheng, Yi Jiang, H. Eric Xu, Youwen Zhuang
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A common mechanism of Sec61 translocon inhibition by small molecules Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-11 Samuel Itskanov, Laurie Wang, Tina Junne, Rumi Sherriff, Li Xiao, Nicolas Blanchard, Wei Q. Shi, Craig Forsyth, Dominic Hoepfner, Martin Spiess, Eunyong Park
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Signal peptide mimicry primes Sec61 for client-selective inhibition Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-11 Shahid Rehan, Dale Tranter, Phillip P. Sharp, Gregory B. Craven, Eric Lowe, Janet L. Anderl, Tony Muchamuel, Vahid Abrishami, Suvi Kuivanen, Nicole A. Wenzell, Andy Jennings, Chakrapani Kalyanaraman, Tomas Strandin, Matti Javanainen, Olli Vapalahti, Matthew P. Jacobson, Dustin McMinn, Christopher J. Kirk, Juha T. Huiskonen, Jack Taunton, Ville O. Paavilainen
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Author Correction: Ancient defensive terpene biosynthetic gene clusters in the soft corals. Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-06-01 Paul D Scesa,Zhenjian Lin,Eric W Schmidt
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Engineered bacterial swarm patterns as spatial records of environmental inputs Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-04 Anjali Doshi, Marian Shaw, Ruxandra Tonea, Soonhee Moon, Rosalía Minyety, Anish Doshi, Andrew Laine, Jia Guo, Tal Danino
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MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-04 Esam T. Abualrous, Sebastian Stolzenberg, Jana Sticht, Marek Wieczorek, Yvette Roske, Matthias Günther, Steffen Dähn, Benedikt B. Boesen, Marcos Martínez Calvo, Charlotte Biese, Frank Kuppler, Álvaro Medina-García, Miguel Álvaro-Benito, Thomas Höfer, Frank Noé, Christian Freund
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Metabolic regulation of epigenetic drug resistance Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-01 Nathaniel W. Snyder, Jordan L. Meier
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Acetyl-CoA biosynthesis drives resistance to histone acetyltransferase inhibition Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-05-01 Timothy R. Bishop, Chitra Subramanian, Eric M. Bilotta, Leopold Garnar-Wortzel, Anissa R. Ramos, Yuxiang Zhang, Joshua N. Asiaban, Christopher J. Ott, Charles O. Rock, Michael A. Erb
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Secrete and protect Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-28 Caitlin Deane
Probiotic bacterial strains such as Escherichia coli Nissle are potentially useful for the targeted delivery of therapeutic molecules to disease sites. However, current strategies for ensuring that these Gram-negative strains deliver their cargo are mostly limited to programmed lysis or display on the outer surface of the bacteria. To promote the release of therapeutic proteins from E. coli Nissle
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Float like a butterfly, sting like a tree Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-28 Benjamin McIlwain
Australia is home to the stinging nettle tree (Dendrocnide excelsa), which is full of excelsatoxin (ExTxA), a peptide structurally reminiscent of spider and cone-snail venoms known to target voltage-gated sodium channels (NaV). The leaves of this plant are covered in dense, toxin-laden trichomes that can cause excruciating pain that lasts for weeks.
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Fungal FKS in focus Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-28 Caitlin Deane
Now, using cryo-electron microscopy, Hu et al. have determined the structure of FKS1 from Saccharomyces cerevisiae. FKS1 consists of a wedge-shaped transmembrane (TM) domain of 17 helices, cytoplasmic GT and accessory (AC) domains, and several unstructured extracellular loops. The TM domain contains multiple bound lipids that probably contribute to stabilization, as well as a pair of pockets, one each
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Matchmaking in the chambers Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-28 Grant Miura
Original reference: Science 379, 996–1003 (2023)
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Cryptic targeting Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-28 Yiyun Song
TDP-43 is an RNA-binding protein that forms toxic aggregates in the neuronal cytoplasm that are commonly detected in multiple neurodegenerative diseases. Mislocalization of TDP-43 to the cytoplasm is thought to disrupt RNA processing, which may also contribute to its pathological effects. Loss of nuclear TDP-43 causes alternative splicing of the gene STMN2, which encodes stathmin-2, a key protein that
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Cascading conjugates Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-28 Russell Johnson
Fabricating site-specific protein conjugates is important for the development of protein therapeutics and uniform constructs that can be used to study function. Chemical ligation is one way to modify proteins; another is to use peptide ligases — such as sortase A, or peptidyl asparaginyl ligases (PALs) — which offer the benefits of enzymatic catalysis. PALs have a much higher catalytic efficiency than
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DNA damage twists base choreography Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-24 Serge L. Smirnov
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Dynamic basis for dA•dGTP and dA•d8OGTP misincorporation via Hoogsteen base pairs Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-24 Stephanie Gu, Eric S. Szymanski, Atul K. Rangadurai, Honglue Shi, Bei Liu, Akanksha Manghrani, Hashim M. Al-Hashimi
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Dissecting the conformational complexity and mechanism of a bacterial heme transporter Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-24 Di Wu, Ahmad R. Mehdipour, Franziska Finke, Hojjat G. Goojani, Roan R. Groh, Tamara N. Grund, Thomas M. B. Reichhart, Rita Zimmermann, Sonja Welsch, Dirk Bald, Mark Shepherd, Gerhard Hummer, Schara Safarian
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The relaxin receptor RXFP1 signals through a mechanism of autoinhibition Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-20 Sarah C. Erlandson, Shaun Rawson, James Osei-Owusu, Kelly P. Brock, Xinyue Liu, Joao A. Paulo, Julian Mintseris, Steven P. Gygi, Debora S. Marks, Xiaojing Cong, Andrew C. Kruse
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Spatial transcriptome uncovers rich coordination of metabolism in E. coli K12 biofilm Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-13 Tianmin Wang, Ping Shen, Yihui He, Yuzhen Zhang, Jintao Liu
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Repurposing degradation pathways for modular metabolite biosynthesis in nematodes Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-06 Chester J. J. Wrobel, Frank C. Schroeder
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Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-04-06 Huilin Yang, Umut Y. Ulge, Alfredo Quijano-Rubio, Zachary J. Bernstein, David R. Maestas, Jung-Ho Chun, Wentao Wang, Jian-Xin Lin, Kevin M. Jude, Srujan Singh, Brian T. Orcutt-Jahns, Peng Li, Jody Mou, Liam Chung, Yun-Huai Kuo, Yasmin H. Ali, Aaron S. Meyer, Warren L. Grayson, Nicola M. Heller, K. Christopher Garcia, Warren J. Leonard, Daniel-Adriano Silva, Jennifer H. Elisseeff, David Baker, Jamie
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Do lipids tune B cell signaling? Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-30 Iztok Urbančič, Christian Eggeling, Erdinc Sezgin
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Membrane phase separation drives responsive assembly of receptor signaling domains Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-30 Sarah A. Shelby, Ivan Castello-Serrano, Kathleen C. Wisser, Ilya Levental, Sarah L. Veatch
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Quantitative profiling of pseudouridylation landscape in the human transcriptome Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-30 Meiling Zhang, Zhe Jiang, Yichen Ma, Wenqing Liu, Yuan Zhuang, Bo Lu, Kai Li, Jinying Peng, Chengqi Yi
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Structural basis for translation inhibition by the glycosylated drosocin peptide Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-30 Timm O. Koller, Martino Morici, Max Berger, Haaris A. Safdari, Deepti S. Lele, Bertrand Beckert, Kanwal J. Kaur, Daniel N. Wilson
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Inhibition of translation termination by the antimicrobial peptide Drosocin Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-30 Kyle Mangano, Dorota Klepacki, Irueosa Ohanmu, Chetana Baliga, Weiping Huang, Alexandra Brakel, Andor Krizsan, Yury S. Polikanov, Ralf Hoffmann, Nora Vázquez-Laslop, Alexander S. Mankin
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Hooking the nucleosome Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-29 Grant Miura
Original reference: Science 379, 717–723 (2023).
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Cyclic nucleotides in for the kill Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-29 Benjamin McIlwain
Antiviral cyclic nucleotides and oligonucleotides are utilized by various organisms for innate immune signaling; in humans, these molecules activate the STING-dependent interferon pathway, whereas bacteria utilize ancestral cGAS/DncV-like nucleotidyltransferases (CD-NTases) to fight bacteriophage infection. Although the molecular basis of eukaryotic innate immune signaling is known, details of its
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One-site ‘-omics’ Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-29 Yiyun Song
Metabolites such as short-chain fatty acids can interact with chromatin and affect transcription by modifying histone proteins. The variety of histone modifications makes it technically hard to delineate their function in a site- and modification-type-specific way. Qin et al. developed a single-site-resolved multi-omics (SiTomics) strategy based on genetic code expansion technology to profile the interacting
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Inositol incorporation intervention Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-29 Caitlin Deane
Original reference: ACS Chem. Biol. 18, 595–604 (2023).
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Monoterpene metabolism unmasked Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-29 Russell Johnson
The leaves of the tree Mitragyna speciosa (also known as kratom) contain a complex mixture of monoterpene indole alkaloids, including one called mitragynine. Mitragynine has pain-relieving effects similar to those of opioid drugs, which has led to the use of kratom as a natural remedy for pain and the management of opioid dependence. However, the biosynthesis of mitragynine is not fully understood
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State of play Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-29 Grant Miura
NRF2 is a transcription factor that promotes the expression of genes encoding anti-oxidant molecules under conditions of high oxidative stress. NRF2 is normally restrained through interactions with KEAP1 under low stress, which promotes NRF2 degradation. Increased levels of NRF2 were thought to enable cancer cells and tumors to tolerate high levels of reactive oxygen species to survive and proliferate
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A community Biased Signaling Atlas Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-27 Jimmy Caroli, Alibek Mamyrbekov, Kasper Harpsøe, Sahar Gardizi, Linda Dörries, Eshan Ghosh, Alexander S. Hauser, Albert J. Kooistra, David E. Gloriam
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A goldilocks amount of H3K27me3 Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-27 Tyler J. Reich, Peter W. Lewis
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Drug addiction unveils a repressive methylation ceiling in EZH2-mutant lymphoma Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-27 Hui Si Kwok, Allyson M. Freedy, Allison P. Siegenfeld, Julia W. Morriss, Amanda L. Waterbury, Stephen M. Kissler, Brian B. Liau
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Cytosolic and mitochondrial NADPH fluxes are independently regulated Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-27 Xiangfeng Niu, Ethan Stancliffe, Susan J. Gelman, Lingjue Wang, Michaela Schwaiger-Haber, Joe L. Rowles, Leah P. Shriver, Gary J. Patti
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Unbalanced response to growth variations reshapes the cell fate decision landscape Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-23 Jingwen Zhu, Pan Chu, Xiongfei Fu
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Proteoforms feel the heat Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-20 Teagan L. Campbell, Bryon S. Drown
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Deep thermal profiling for detection of functional proteoform groups Nat. Chem. Biol. (IF 16.174) Pub Date : 2023-03-20 Nils Kurzawa, Isabelle Rose Leo, Matthias Stahl, Elena Kunold, Isabelle Becher, Anastasia Audrey, Georgios Mermelekas, Wolfgang Huber, André Mateus, Mikhail M. Savitski, Rozbeh Jafari