Rationally seeded computational protein design of ɑ-helical barrels
Nature Chemical Biology
by Katherine I. Albanese, Rokas Petrenas, Fabio Pirro, Elise A. Naudin, Ufuk Borucu, William M. Dawson, D. Arne Scott, Graham. J. Leggett, Orion D. Weiner, Thomas A. A. Oliver, Derek N. Woolfson
1d ago
Nature Chemical Biology, Published online: 20 June 2024; doi:10.1038/s41589-024-01642-0 An efficient computational pipeline starting from validated peptide assemblies has been used to design two families of α-helical barrel proteins with functionalizable channels. This rationally seeded computational protein design approach delivers soluble, monomeric proteins that match the design targets accurately and with high success rates ..read more
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3-Hydroxykynurenine targets kainate receptors to promote defense against infection
Nature Chemical Biology
by Margarita Parada-Kusz, Anne E. Clatworthy, Emily R. Goering, Stephanie M. Blackwood, Jack Y. Shigeta, Eivgeni Mashin, Elizabeth J. Salm, Catherine Choi, Senya Combs, Jenny S. W. Lee, Carlos Rodriguez-Osorio, Clary Clish, Susumu Tomita, Deborah T. Hung
1d ago
Nature Chemical Biology, Published online: 19 June 2024; doi:10.1038/s41589-024-01635-z A tryptophan metabolite was identified that acts systemically to promote defense against bacterial infection by targeting kainate receptors (KARs), revealing a novel intersection between tryptophan metabolism and KARs in immune defense ..read more
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Channeling kynurenine
Nature Chemical Biology
by Mollie I. Sweeney, David M. Tobin
1d ago
Nature Chemical Biology, Published online: 19 June 2024; doi:10.1038/s41589-024-01643-z An in vivo chemical screen has uncovered a potential role for a tryptophan metabolite in promoting host survival during bacterial infections through modulation of ionotropic glutamate receptors. Host-directed therapies for bacterial infections offer a largely untapped approach to treatment ..read more
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Quantitative control of subcellular protein localization with a photochromic dimerizer
Nature Chemical Biology
by Takato Mashita, Toshiyuki Kowada, Hayashi Yamamoto, Satoshi Hamaguchi, Toshizo Sato, Toshitaka Matsui, Shin Mizukami
1d ago
Nature Chemical Biology, Published online: 18 June 2024; doi:10.1038/s41589-024-01654-w A photochromic dimerizer was developed for light-controlled reversible and quantitative regulation of intracellular protein localization, enabling optical control of PTEN-induced kinase 1 (PINK1)–Parkin-mediated mitophage induction ..read more
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Architecture of the RNF1 complex that drives biological nitrogen fixation
Nature Chemical Biology
by Lin Zhang, Oliver Einsle
1d ago
Nature Chemical Biology, Published online: 18 June 2024; doi:10.1038/s41589-024-01641-1 Biological nitrogen fixation requires low-potential electrons from ferredoxin or flavodoxin. Here the authors show how the soil diazotroph Azotobacter vinelandii employs the NADH:ferredoxin oxidoreductase RNF1 complex to lower the midpoint potential of the electron from NADH to reduce ferredoxin ..read more
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The realization of CRISPR gene therapy
Nature Chemical Biology
by Yitong Ma, Lei S. Qi
1w ago
Nature Chemical Biology, Published online: 13 June 2024; doi:10.1038/s41589-024-01645-x The inaugural CRISPR-based drug Casgevy has been approved by several medical agencies, with other CRISPR-based therapies currently in clinical trials. Although there are technological hurdles to overcome, chemical biology has a vital role in developing recent breakthroughs in base editing, prime editing and epigenetic editing into future treatments ..read more
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Optimizing multicopy chromosomal integration for stable high-performing strains
Nature Chemical Biology
by Fei Du, Zijia Li, Xin Li, Duoduo Zhang, Feng Zhang, Zixu Zhang, Yingshuang Xu, Jin Tang, Yongqian Li, Xingxu Huang, Yang Gu, Xiaoman Sun, He Huang
1w ago
Nature Chemical Biology, Published online: 10 June 2024; doi:10.1038/s41589-024-01650-0 An end-to-end pipeline generates the optimal copy number combination of genes in a biosynthetic pathway for chromosomal integration to engineer high-performing strains with genetic stability ..read more
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A de novo designed coiled coil-based switch regulates the microtubule motor kinesin-1
Nature Chemical Biology
by Jessica A. Cross, William M. Dawson, Shivam R. Shukla, Johannes F. Weijman, Judith Mantell, Mark P. Dodding, Derek N. Woolfson
1w ago
Nature Chemical Biology, Published online: 07 June 2024; doi:10.1038/s41589-024-01640-2 The kinesin-1 motor protein accesses open active and closed autoinhibited states. These states are regulated by a flexible elbow within a complex coiled-coil architecture. Now, a conformational switch has been developed by engineering the elbow to create a closed state that can be controllably opened with a de novo designed peptide to increase kinesin transport inside cells ..read more
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High-resolution structure of a novel fluorogenic RNA aptamer
Nature Chemical Biology
by
2w ago
Nature Chemical Biology, Published online: 06 June 2024; doi:10.1038/s41589-024-01652-y Fluorogenic RNA aptamers have previously been developed to enhance RNA imaging. We determined the tertiary complex structures of a newly discovered Clivia aptamer, which exhibits a small size and a large Stokes shift. Structural insights into the fluorescence activation mechanism of Clivia build a strong foundation for its efficient use in RNA imaging ..read more
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Mechanisms of neutralization of toxSAS from toxin–antitoxin modules
Nature Chemical Biology
by Lucia Dominguez-Molina, Tatsuaki Kurata, Albinas Cepauskas, Dannele Echemendia-Blanco, Safia Zedek, Ariel Talavera-Perez, Gemma C. Atkinson, Vasili Hauryliuk, Abel Garcia-Pino
2w ago
Nature Chemical Biology, Published online: 04 June 2024; doi:10.1038/s41589-024-01630-4 Toxic small alarmone synthetase (toxSAS) enzymes are toxic effectors of certain toxin–antitoxin modules, involved in phage defense and secretion systems. Here the authors establish the mechanism underlying toxSAS inhibition by structured antitoxins and reveal the connection between neutralization strategy and substrate specificity ..read more
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