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The ability to alter cell identity with small molecules represents a powerful approach to restore biological function lost because of cellular deficiency. Developing this capability through advances in chemical biology could have an enormous impact on human health.
The glucose-based polymer cellulose is of great biological and economical importance; however, little is known about how cellulose is synthesized. Now, structural estimates of one of the cellulose-synthesizing subunits in the bacterium Acetobacter xylinum help to explain the extrusion of the newly synthesized glucan chains.
Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level.
Hyper-performing whole-cell catalysts are required for the renewable and sustainable production of petrochemical replacements. Chassis cells—self-replicating minimal machines that can be tailored for the production of specific chemicals—will provide the starting point for designing these hyper-performing 'turbo cells'.
A new method to monitor interactions between cell surface proteins reveals that interaction of the neuronal cell surface adhesion proteins neurexin and neuroligin is increased at synapses during a stimulus or developmental activity. This increased activity-dependent surface density of neurexin–neuroligin complexes is subsequently required for maturation of synapses.
Some of the most celebrated triumphs of chemical biology are molecularly targeted therapeutics to combat human disease. However, a grand challenge looms as informative diagnostic strategies must be developed to realize the full impact of these promising pharmaceutical agents.
In the postsequencing era, chemical biology is uniquely situated to investigate genomic DNA alterations arising through epigenetic modifications, genetic rearrangements or active mutation. These transformations significantly expand nature's diversity and may profoundly alter our view of DNA's coding potential.
Chemical biology is now able to discover molecules that manipulate virtually any biological target or process. It remains a grand challenge to leverage these molecules into useful probes that can be used to address unsolved problems in biology.
Rationally designing new strategies to control the human immune response stands as a key challenge for the scientific community. Chemical biologists have the opportunity to address specific issues in this area that have important implications for both basic science and clinical medicine.
The synthesis and biological annotation of small molecules from underexplored chemical space will play a central role in the development of drugs for challenging targets currently being identified in frontier areas of biological research such as human genetics.
Variations between single members of a bacterial population can lead to antibiotic resistance that is not gene based. The future of effective infectious disease management might depend on a better understanding of this phenomenon and the potential to manipulate both it and microbial population dynamics in general.
Engineering biosynthetic pathways to natural products is a challenging endeavor that promises to provide new therapeutics and tools to manipulate biology. Information-guided design strategies and tools could unlock the creativity of a wide spectrum of scientists and engineers by decoupling expertise from implementation.
Cardiac glycosides, which target the Na+–K+–ATPase, block IFNβ expression by increasing intracellular Na+ levels to inhibit the ATPase activity of the RNA sensor RIG-I, affecting the signaling cascade downstream.
Fluorescent high-affinity activity-based probes used to monitor the activity and presence of active glucocerebrosidase in vitro and in vivo help in understanding Gaucher disease and its treatment with pharmacological chaperones.
Expression of a Huntington's-disease variant of huntingtin protein causes accumulation of the chaperone protein disulfide isomerase. This protein is the target of compounds obtained from screening for those that can alleviate cell death promoted by the mutant huntingtin, and represents a new connection between protein misfolding and cell death.
Free-energy molecular dynamics simulations and high-resolution structural analysis of the c-ring of the F1Fo ATPase rotary motor, which mediates ion translocation, suggest conformational flexibility and reversible ion binding in the c-subunits, in an environment mimicking the a-subunit.
Ten significantly active new (R)-transaminases, still very rare enzymes, were found among 21 designed variants obtained from nothing more than existing transaminase structures and alignment of pertinent fingerprints of annotated sequences.
Aminoacylation of tRNA is the cellular process for providing aminoacyl donors for the ribosome synthesis of polypeptides. New research highlights an unexpected structural overlap between enzymes involved in this process and those involved in the biosynthesis of cyclodipeptides, an important class of bioactive molecules.
