Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

March 5th, 2018 by Lara N. Gechijian

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands, Published online: 05 March 2018; doi:10.1038/s41589-018-0010-y

Selective TRIM24 degradation is achieved by co-opting the VHL E3 ubiquitin ligase machinery. TRIM24 degradation outperforms bromodomain inhibition, with an enhanced antiproliferative effect in acute leukemia, a novel context of TRIM24 dependency.
  • Posted in Nat Chem Biol, Publications
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A lanthipeptide library used to identify a protein–protein interaction inhibitor

March 5th, 2018 by Xiao Yang

A lanthipeptide library used to identify a protein–protein interaction inhibitor

A lanthipeptide library used to identify a protein–protein interaction inhibitor, Published online: 05 March 2018; doi:10.1038/s41589-018-0008-5

The substrate-tolerant lanthipeptide synthetase ProcM enables the construction of a plasmid-encoded library of bicyclic lanthipeptides, from which an inhibitor of the p6–UEV protein–protein interaction is identified by a reverse two-hybrid screen.
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Regulation of apoptosis by an intrinsically disordered region of Bcl-xL

March 5th, 2018 by Ariele Viacava Follis

Regulation of apoptosis by an intrinsically disordered region of Bcl-xL

Regulation of apoptosis by an intrinsically disordered region of Bcl-xL, Published online: 05 March 2018; doi:10.1038/s41589-018-0011-x

Post-translational modification of residues in an intrinsically disordered region of Bcl-XL promotes interactions with its folded core and allosterically reduces affinity for proapoptotic BH3-domain-containing proteins, resulting in apoptosis.
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Trp-ing upon new repressors

February 26th, 2018 by Andreas K. Brödel

Trp-ing upon new repressors

Trp-ing upon new repressors, Published online: 26 February 2018; doi:10.1038/s41589-018-0012-9

Bioengineers have used directed evolution to generate a new family of synthetic transcription factors based on the tryptophan repressor. The evolved repressor family enables researchers to build new gene circuits for biomedical applications.

Directed evolution of a synthetic phylogeny of programmable Trp repressors

February 26th, 2018 by Jared W. Ellefson

Directed evolution of a synthetic phylogeny of programmable Trp repressors

Directed evolution of a synthetic phylogeny of programmable Trp repressors, Published online: 26 February 2018; doi:10.1038/s41589-018-0006-7

Directed evolution of Trp repressor (TrpR) variants that are responsive to halogenated tryptophan analogs and recognize new operator sites serve as useful components for constructing complex gene expression networks.
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Resistance to nonribosomal peptide antibiotics mediated by <span class=”small-caps”>d</span>-stereospecific peptidases

February 26th, 2018 by Yong-Xin Li

Resistance to nonribosomal peptide antibiotics mediated by d-stereospecific peptidases

Resistance to nonribosomal peptide antibiotics mediated by <span class="small-caps">d</span>-stereospecific peptidases, Published online: 26 February 2018; doi:10.1038/s41589-018-0009-4

Networking-associated genome mining on bacterial genomes followed by chemical and enzymatic analysis identified a mechanism of resistance toward nonribosomal peptide antibiotics based on hydrolytic cleavage by d-stereospecific peptidases.
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A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

February 26th, 2018 by Kiryl D. Piatkevich

A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters, Published online: 26 February 2018; doi:10.1038/s41589-018-0004-9

Directed evolution of opsins via robotic high-content screening finds a fluorescent reporter of voltage that is simultaneously optimized for brightness, localization and voltage sensitivity and is applicable in three model systems.
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Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases

February 19th, 2018 by Lukas Reisky

Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases

Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases, Published online: 19 February 2018; doi:10.1038/s41589-018-0005-8

The discovery of cytochrome P450 monooxygenases that catalyze oxidative demethylation of 6-O-methyl-d-galactose reveals a new activity of cytochrome P450 enzymes and their role in polysaccharide biomass degradation in marine bacteria.
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Protein evolution: Hacking an enzyme

February 14th, 2018 by Kristoffer E Johansson

Protein evolution: Hacking an enzyme

Protein evolution: Hacking an enzyme, Published online: 14 February 2018; doi:10.1038/nchembio.2574

Early stages of protein evolution are inherently difficult to study. Genetic selection in Escherichia coli has now identified a life-sustaining de novo enzyme arising from a simple scaffold that is completely different from the native enzyme.

Altering form for function

February 14th, 2018 by Nature Chemical Biology - Issue - nature.com science feeds

Altering form for function

Altering form for function, Published online: 14 February 2018; doi:10.1038/nchembio.2582

Elucidating the mechanisms by which biomolecules are chemically modified and how these alterations regulate biological pathways represents a leading frontier in chemical biology.