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There are many techniques that can be employed to control gene expression at the post-translational level. However, a novel system called SMASh (small molecule–assisted shutoff), which allows for chemically-induced degradation of target proteins, presents some distinct advantages.
The complex flavonoid montbretin A (MbA) is a powerful inhibitor of human pancreatic amylase (HPA) and a potential tool in the treatment of type 2 diabetes. The X-ray structure of the MbA–HPA complex now shows that a hydrophobic collapse of two phenol fragments in the structure of MbA is key to its activity.
Many peptide-based natural products require a leader peptide to reach their final modified form, but the identification of general rules for leader peptide interactions have been stymied by the diversity of these molecules. Two papers reporting crystallographic and bioinformatic analysis of these systems now reveal a structurally conserved domain that mediates leader peptide binding.
A small molecule targeting the protein-protein interaction between a chromatin binding protein and an oncogenic transcription factor shows therapeutic potential in a subtype of acute myeloid leukemia.
A powerful, high-throughput single-molecule approach to probe the nanoscale mechanical properties of the Tus–Ter protein–DNA complex reveals that the Tus–Ter-induced lock in unzipping at the nonpermissive face requires only DNA strand separation and involves a progressive strengthening of the Tus–Ter complex.
The spliceosome is an immensely complex molecular machine tasked with stitching together coding regions of genes. New work reveals how a small molecule can affect this machinery in a model of spinal muscular atrophy, a disease linked to aberrant splicing.
Sulfide signaling is biologically important, but the identity and source of reactive sulfur species (RSS) remains unclear. An analysis of sulfur reactivity now suggests that oxidation pathways thought to dispose of sulfur may actually create RSS.
The molecular basis of biomaterial assembly and function can provide inspiration for new materials science designs. New research explains the squid beak's transition from soft to hard through the identification of two new families of proteins with unusual physical properties.
A modified amphotericin antifungal that is less toxic to human cells, owing to its increased preference for its fungal ergosterol target versus human cholesterol, can still evade the evolution of resistance.
The ability to vary a drug's residence time on a target is important for drug optimization. A series of reversible covalent inhibitors of select kinases demonstrates the feasibility of tuning residence time from minutes to days through modification of noncovalent features of the molecules.
Biosensors are emerging as an important tool to evolutionarily engineer metabolic pathway enzymes for the microbial production of chemicals. A colorimetric biosensor used to increase dopamine levels in yeast now enables the production of benzylisoquinoline alkaloids from glucose.
One-carbon metabolic pathways create new opportunities for metabolic engineering, but natural pathways have limitations in catalytic efficiency and interspecies transferability. Now a computationally designed enzyme, formolase, enables the construction of a synthetic metabolic pathway in Escherichia coli for assimilation of formate into a glycolytic intermediate in only five reaction steps.
This Perspective discusses recent advances in high-throughput omics approaches such as proteomic and interactome profiling and genetic perturbations that allow the identification and alterations of cell signaling networks.
Binding kinetics (BK) has an indispensable role in pharmacodynamics (PD). Incorporating slow BK into a mechanistic PD model is shown to have predictive value for in vitro cellular and in vivo animal antibacterial efficacy.
Spider silks have enormous potential as strong yet flexible biomaterials, but obtaining artificial silk polymers has proven challenging. Recent advances in our understanding of natural silk processing may inform techniques for silk production.
