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Identifying new proteoforms — structural variants of proteins — is frequently challenging, particularly on the proteome-wide scale. A new study leverages their differential thermal stabilities to identify proteoform functional groups by deep thermal proteome profiling.
Applying thermal proteome profiling to acute B cell childhood leukemia cell lines combined with deep peptide fractionation and a graph-based clustering algorithm allows inference of functional proteoform groups and their association with drug response.
A new review article details how new structural insight regarding modular polyketide synthases (PKSs) helps us better understand the organization of catalytic events within a PKS module. The plausible models discussed will likely influence future PKS engineering efforts.
Engineering synthetic tools that facilitate decision-making in mammalian cells could enable myriad biomedical applications. Researchers have now developed a new system of inducer-controlled transcription factors to facilitate synthetic decision-making (LOGIC) in human cells based on modular protein-fusion cascades.
Live-cell HRMAS NMR spectroscopy and genome-scale metabolic modeling enable high-resolution analysis of dynamic, anaerobic metabolism in Clostridioides difficile, identifying the confluence of carbohydrate and amino acid fermentations for alanine synthesis.
Kim et al. used directed evolution methods to identify a high-fidelity SpCas9 variant, Sniper2L, which exhibits high general activity but maintains high specificity at a large number of target sites.
The authors show modular functionality of TetR-like proteins in mammalian cells, separating the protein–DNA and the protein–protein interaction. This allows for engineered ON- and OFF-type responses to stimuli, higher order and multi-input logics.
A chemically controlled Cas9 switch offers a simple, general approach to temporal control of Cas9 effectors, including transcriptional activators, base editors and a prime editor. Chemically controlled base editors revealed bystander editing kinetics.
Using an integrated metabologenomics approach, the biosynthetic pathway for the pestalamides is revealed and over 200 high-confidence targets are identified for future studies.
We identified small molecules that rewire the transcriptional state of cancer cells by covalently targeting the RNA-binding protein NONO. These small molecules stabilize the interactions of NONO with its target mRNAs, thereby overriding the compensatory action of paralog proteins and revealing a pharmacological strategy for disrupting previously undruggable oncogenic pathways.
Integrated phenotypic screening and activity-based protein profiling identifies small molecules that decrease the expression of oncogenic transcription factors and suppress cancer cell growth by covalently targeting the RNA-binding protein NONO.
Bifidobacterium bifidum is a member of the human gut microbiome. A new report demonstrates that it can degrade sulfated mucin O-glycans in vivo, and a GH20 sulfoglycosidase possessing a novel GlcNAc-6S-specific carbohydrate-binding module plays a pivotal role.
