Published today in @natchembio.nature.com @natureportfolio.nature.com: a framework for the de novo design of antimicrobial α-helical peptides that assemble into transmembrane barrel-stave nanopores.
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Small molecules can covalently modify proteins and generate covalent neoantigens, triggering immune responses. Now, a chemoproteomic platform enables the discovery of covalent neoantigens, which can also be harnessed for immunotherapeutic applications www.nature.com/articles/s41...
Expanding the repertoire of chemically induced covalent neoantigens - Nature Chemical Biology
Small molecules can covalently modify proteins to generate hapten-modified peptides, triggering T cell-mediated immune responses. Now a chemoproteomic platform enables the discovery of covalent neoant...
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Check out our Editorial “Computing complexity” which refers to both modeling biological complexity and the computational challenges www.nature.com/articles/s41...
Nature Chemical Biology@natchembio.nature.com · 6d agoOur August issue is live and is a Focus on computational work guiding biological discovery! www.nature.com/nchembio/vol... The cover image depicts a computational-experimental approach to distinguish lipid solvation vs. lipid-ligand binding in membrane protein function
Our August issue is live and is a Focus on computational work guiding biological discovery! www.nature.com/nchembio/vol... The cover image depicts a computational-experimental approach to distinguish lipid solvation vs. lipid-ligand binding in membrane protein function
An active learning approach integrating explainable machine learning, Bayesian optimization, and high-throughput community construction designs microbial communities with desired functions in response to key nutrients www.nature.com/articles/s41...
Designing fiber–gut microbiome interactions with active learning - Nature Chemical Biology
Dietary fibers are a primary energy source for gut bacteria and shape the composition and function of the microbiome. Now, an active learning approach integrating explainable machine learning, Bayesia...
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Enantioselective transcription factors are evolved that convert chiral reaction products into fluorescent signals, enabling the screening and evolution of asymmetric enzymes with inverted selectivity www.nature.com/articles/s41...
Using enantioselective biosensors to evolve asymmetric biocatalysts - Nature Chemical Biology
Here d’Oelsnitz et al. generate enantioselective transcription factors that convert chiral reaction products into fluorescent signals, enabling the rapid evolution of asymmetric enzymes with inverted ...
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New-to-nature nanomaterials can irreversibly accumulate in cells and induce cell stress. Now, peptide assemblies have been designed that morphologically transform in influx-efflux cycles in response to restoring redox homeostasis in bacterial cells www.nature.com/articles/s41...
Restoring intracellular homeostasis disrupted by synthetic nanoassemblies - Nature Chemical Biology
Cells have evolved defense pathways to maintain homeostasis against external perturbations, but not against new-to-nature nanomaterials, which can irreversibly accumulate and induce cell stress. Now, ...
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Host antimicrobial peptides (AMPs) are a frontline defense against infection. A new paper shows maturation of AMP repertoires early in life can predict stable coexistence with a highly invasive pathogen www.nature.com/articles/s41...
Early maturation of host antimicrobial peptide defences is associated with host–pathogen coexistence - Nature Chemical Biology
Host antimicrobial peptides (AMPs) are a frontline defense against infection. Now, it has been shown that maturation of AMP repertoires early in life can predict stable host coexistence with a highly ...
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Synthetic receptors enable high-resolution enrichment of ultralow-abundance phosphopeptide positional isomers from complex human proteomes www.nature.com/articles/s41...
Proteoform-specific enrichment of phosphopeptide isomers by polymer-based synthetic receptors - Nature Chemical Biology
Resolution of protein phosphorylation at specific sites is challenging. Now, synthetic receptors have been developed that enable high-resolution enrichment of ultralow-abundance phosphopeptide positio...
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Protein stability is determined by single-site bias rather than pairwise covariance www.nature.com/articles/s41...
Protein stability is determined by single-site bias rather than pairwise covariance - Nature Chemical Biology
Sequence biases at individual positions can be used to design more stable protein variants, while correlation between pairs of residues has also been shown to be important for specifying protein struc...
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Tumor immune cell targeting chimeras (TICTACs) reprogram tumor-associated macrophages www.nature.com/articles/s41...
Tumor immune cell targeting chimeras reprogram tumor-associated macrophages - Nature Chemical Biology
Tumor-associated macrophages (TAMs) predominantly adopt an M2-like pro-tumor phenotype, promoting anti-inflammatory signaling and cancer cell metastasis. Now, tumor immune cell targeting chimeras enab...
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Structures of cannabinoid cyclase show that bacterial and plant cyclases use distinct mechanisms for cannabinoid synthesis, and variants are engineered with improved stereocontrol www.nature.com/articles/s41...
Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes - Nature Chemical Biology
Cannabinoid cyclases produce bioactive cannabinoids, but their mechanisms are poorly understood. Here the authors solve the substrate-bound structure of a cannabinoid cyclase, show that bacterial and ...
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A new paper reports a root-tip-specific biosynthetic pathway for the alkaloid core of plant-derived anticancer drug homoharringtonine, identifying six enzymes and seven intermediates www.nature.com/articles/s41...
Cephalotaxinone enzymes reveal a whole plant model for homoharringtonine biosynthesis - Nature Chemical Biology
Homoharringtonine (HHT) is a plant-derived anticancer drug approved by the US Food and Drug Administration. Here, the authors elucidate a root-tip-specific biosynthetic pathway to its alkaloid core, i...
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Allosteric disordering of eIF2B regulates the integrated stress response www.nature.com/articles/s41...
Allosteric disordering of eIF2B regulates the integrated stress response - Nature Chemical Biology
eIF2B is a guanine nucleotide exchange factor that catalyzes GDP/GTP exchange on the translation initiation factor eIF2 to regulate protein synthesis. Using cryo-EM structure-guided biochemistry and p...
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Our July issue is live! www.nature.com/nchembio/vol... The cover image illustrates a nanobody stabilizing a formerly misfolded CFTR chloride channel, thereby enabling functional recovery
A new Perspective on image-guided pharmacotherapy, which holds promise for personalized medicine through confining drug activity precisely to disease areas using electromagnetic irradiation www.nature.com/articles/s41...
Image-guided activation of drugs with electromagnetic radiation - Nature Chemical Biology
Image-guided pharmacotherapy holds great promise for personalized medicine through confining drug activity precisely to the disease area using electromagnetic irradiation. This Perspective describes t...
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Discovery of noncanonical cytochrome P450 enzymes in nature www.nature.com/articles/s41...
Discovery of noncanonical cytochrome P450 enzymes in nature - Nature Chemical Biology
Cytochrome P450s catalyze essential reactions and carry a strictly conserved proximal cysteine ligand. Here, we identify noncanonical P450s that harbor diverse proximal ligands, including serine and s...
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Our paper is now online here: rdcu.be/fpILZ
A ratiometric fluorescent reporter of mitochondrial sodium
Nature Chemical Biology - A ratiometric fluorescent probe that maps absolute mitochondrial Na+ at single-organelle resolution and works independently of membrane potential has now been developed....
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A new paper presents CANVAS, a computational workflow that converts minimal de novo TIM barrels into enzymes by designing structural lids that generate tailored active sites www.nature.com/articles/s41...
Customizing the structure of minimal TIM barrels to craft efficient de novo enzymes - Nature Chemical Biology
The TIM barrel is nature’s most versatile enzyme fold, yet de novo variants lack functional active sites. Minimal de novo TIM barrels have now been converted into enzymes by designing structural lids ...
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PBCNet2.0 predicts relative affinity changes induced by ligand modifications for probe discovery and optimization and shows an emergent capability to predict affinity changes due to binding residue mutations, supporting drug resistance analysis www.nature.com/articles/s41...
Atomic-level protein–ligand recognition with PBCNet2.0 for probe discovery - Nature Chemical Biology
Protein–ligand binding affinity prediction is important for the development and optimization of molecular probes. PBCNet2.0 predicts relative affinity changes induced by ligand modifications (for exam...
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Opposing roles of serine and charge in IDR condensate miscibility www.nature.com/articles/s41...
Opposing roles of serine and charge in IDR condensate miscibility - Nature Chemical Biology
Pei, Wang, Quan and Geng and colleagues reveal how amino acid composition within intrinsically disordered regions influences the miscibility of biomolecular condensates and their function. Serine and ...
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A new paper identifies and characterizes a conserved trypsin-MBL (metallo-β-lactamase) pair in bacterial immunity www.nature.com/articles/s41...
The antiphage mechanism of a widespread trypsin–MBL defense module - Nature Chemical Biology
This study identifies and characterizes a conserved trypsin–MBL (metallo-β-lactamase) pair in bacterial immunity; upon infection, trypsin is activated through inhibitory ATP hydrolysis, subsequently a...
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Cell-type specific bioorthogonal chemistry using enzyme-activated caged tetrazines www.nature.com/articles/s41...
Achieving cell-type-specific bioorthogonal chemistry using enzyme-activated caged tetrazines - Nature Chemical Biology
An enzyme-triggered tetrazine uncaging strategy for cell-selective bioorthogonal chemistry has now been developed. The method called TRACE (tetrazine release and activation by cellular enzymes) enable...
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Structures of telomerase with allosteric inhibitor BIBR1532 reveal an unexpected mode of inhibition and unique insights into telomerase mechanism www.nature.com/articles/s41...
Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition - Nature Chemical Biology
Telomerase, the ribonucleoprotein that maintains telomere ends, is upregulated in most cancer cells, making it a promising oncology target. Cryo-electron microscopy structures of telomerase with allos...
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Glucose deprivation promotes OXCT1 phosphorylation and nuclear translocation, which leads to repressed transcription of MHC-I and chemokine genes and reduced immunotherapy responsiveness www.nature.com/articles/s41...
Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription - Nature Chemical Biology
Metabolic reprogramming in cancer cells can contribute to responsiveness to immunotherapy. In this study, glucose deprivation in hepatocellular carcinoma cells was found to promote OXCT1 S113 phosphor...
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Cystine C-S bond cleavage fuels cysteine production under disulfide reductase deficiency www.nature.com/articles/s41...
Cystine C–S bond cleavage fuels cysteine production under disulfide reductase deficiency - Nature Chemical Biology
Cells reduce the S–S bond in cystine to obtain cysteine. A robust alternative pathway, initiating with enzymatic cleavage of a cystine C–S bond followed by nonenzymatic reactions, is here shown to sup...
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Happy to share the latest macrocycle paper from the Heinis lab, which I was happy to play a small part in during my postdoc. Big congrats to co-first authors Xinjian and Lluc. Now out in @natchembio.nature.com www.nature.com/articles/s41...
Generation of membrane-permeable cyclic peptides inhibiting protein–protein interaction - Nature Chemical Biology
Membrane-permeable cyclic peptides offer access to difficult intracellular targets but discovery remains challenging. Here the authors show that cell-active cyclic peptides can be identified by screen...
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A new paper reports identification of a binder of IRF4 and development of a selective degrader that exhibits strong cytotoxicity against multiple myeloma cell lines www.nature.com/articles/s41...
Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma - Nature Chemical Biology
Identification of a binder of interferon regulatory factor 4 (IRF4) enabled development of a selective degrader, dIRF4-2, that exhibited strong cytotoxicity in multiple myeloma cell lines, offering an...
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Oxygen-dependent and photoreactive APEX2-based proximity labeling using a chemically evolved biotin probe for applications in living cells and in vivo www.nature.com/articles/s41...
H2O2-free proximity proteomics for exploring dynamic protein complexes in living systems - Nature Chemical Biology
The H2O2 dependence of APEX2 and the toxicity of H2O2 hinder the use of APEX2-based proximity labeling in vivo. Now, APEX2 is rendered blue light activated with oxygen-dependent and low-H2O2-responsiv...
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A new Review on using large-scale glycomics to understand glycan function #glycotime www.nature.com/articles/s41...
Large glycomics datasets as a tool to understand the function of glycans - Nature Chemical Biology
Recent technological advances are enabling a growing number of large-scale glycomics studies. This Review discusses the challenges in high-throughput glycoanalytical methods with special attention to ...
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