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Diversity in the function of nucleic acids, proteins and other biological macromolecules is due in large part to the chemical modifications that they undergo during their biosynthesis and as they take part in their biological functions. The collection of pieces in this themed issue highlights the structural and functional importance of several post-translational modifications of proteins, as well as chemical modifications of nucleic acids, lipids, and carbohydrates. The cover image depicts a subset of the myriad chemical modifications explored in this issue as pattern pieces that are used to tailor biological macromolecules. Cover art by Erin Dewalt.
Elucidating the mechanisms by which biomolecules are chemically modified and how these alterations regulate biological pathways represents a leading frontier in chemical biology.
Post-translational modifications (PTMs) are ubiquitous in all forms of life and often modulate critical protein functions. Recent chemical and biological advances have finally enabled scientists to precisely modify proteins at physiologically relevant positions, ushering in a new era of protein studies.
Mycobacteria produce carbohydrates of exceptional structures that are covalently modified by unique substituents, whose functional characterization could expand our understanding of how mycobacteria adapt to their environment.
RNA structure is irrevocably linked to function. A new method, termed 'LASER', utilizes a light-activated chemical probe to query RNA tertiary structure and illuminate RNA–protein interactions in the living cell.
G-protein-coupled receptors (GPCRs) are critically involved in signal transduction. Structural views of several GPCRs have recently been obtained, but the structural principles determining subtype selectivity are still mostly elusive. Now, a combined solid-state NMR and molecular-modeling approach reveals how bradykinin GPCRs distinguish between closely related peptide ligands.
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.
Technologies for engineering immune cells to recognize features on cancer cells are transforming oncology. Synthetic biologists now expand this approach by conferring therapeutic functions to nonimmune cells and by programming cells to sense and respond to a new class of physiological cues.
A de novo–designed protein, Syn-F4, hydrolyzes the siderophore ferric enterobactin both in vitro and in Escherichia coli cells, enabling a bacterial strain lacking the essential natural enterobactin esterase to grow in iron-limited medium.
An environmentally friendly approach to indigo production is facilitated by the characterization of a plant indoxyl glucosyltransferase, which converts the unstable indoxyl precursor into indican by addition of a glucose protecting group.
A structure of leukotriene B4 receptor BLT1 bound with a benzamidine-containing compound, BIIL260, reveals an inverse-agonist mechanism involving ligand binding in the sodium ion-centered water cluster adjacent to the conserved orthosteric site of class A GPCRs.
A combination of biochemical and structural techniques allows the characterization of a novel docking domain in polyketide synthases, which is structurally disordered and facilitates association of subunits at ketosynthase–dehydratase junctions.
A method called Light Activated Structural Examination of RNA (LASER) enables monitoring of the solvent accessibility of purine nucleobases and identifies rapid structural changes of cellular RNA–protein interactions and intracellular RNA structures.
NMR to resolve the subtype specificity of two peptide ligands for human bradykinin receptors B1R and B2R shows different presentations of the peptide termini toward the receptor and interactions with nonconserved receptor binding-pocket residues.
Combining Drosophila genetics with chemistry and computation led to the development of novel kinase inhibitors based on the RAF-targeting drug sorafenib that reveal the RET oncogene as an enhancer of drug action and improve the therapeutic window in medullary thyroid carcinoma models.
A synthetic, orthogonal pair of the plant hormone auxin and its receptor TIR1 was engineered to hijack auxin signaling without interfering with the endogenous system. The synthetic system conclusively demonstrates the role for TIR1 in auxin-induced acid growth.
A new type of fungal lytic polysaccharide monooxygenase (LPMO) catalyzes the oxidative degradation of xylan components of cellulosic biomass and offers potential in wood biorefining.
Partial substitution of CRISPR RNAs with DNA nucleotides retains CRISPR–Cas9 genome editing activity while enhancing efficiency and specificity within cells, suggesting that DNA–RNA hybrids may be economical reagents for targeted genome editing.
Chimeric antigen receptor (CAR)-expressing T cells were engineered to recognize soluble protein ligands that, by inducing CAR dimerization, mechanically couple ligand binding and receptor signaling to produce immune effector molecules.