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Antimicrobial resistance to currently available antibiotics requires innovation of antibiotics. Here, the authors identify a critical inhibitory site in an energy-producing enzyme, which can lead to rational design of antibiotics.

Separation and analysis of enantiomers is a difficult task due to the normally identical physical properties they display. Here, the authors show how chiral molecules with non-zero dipoles can be propelled in opposite directions under the influence of a rotating electric field.

Organic biocrystals play crucial roles in biological processes and diseases, yet the molecular mechanisms of their formation remain poorly understood. Here, the authors reveal that hematin crystal nucleation in malaria parasites follows a nonclassical pathway and can be modulated by solute-modifier interactions, offering a strategy to control crystal formation in a variety of systems, including for malaria treatment.

In this work, the authors show that two parallel and distinct evolutionary pathways can lead to genetically diverse enzyme species that harbour similar catalytic activities against the desired substrate, modulated by distinct conformational dynamics during catalysis.

Thylakoid K⁺/H⁺ exchange by KEA3 optimizes photosynthesis during light fluctuations. Here, the authors show that a combination of stromal pH, ATP, ADP and NADP⁺, NADPH induces structural re-arrangements required for KEA3 regulation in vivo.

Binding modes of antigenically drifted hemagglutinins of human influenza A viruses have been determined by NMR using synthetic N-glycans having ¹³C-labeled monosaccharides to pinpoint which monosaccharides of extended LacNAc chains engage with the HAs.

Here, the authors design a “beyond aqueous” colloidal electrolyte with ultralow salt concentration and inherent low freezing point and investigate its colloidal behaviors and underlying mechanistic principles to stabilize cryogenic Zn metal battery.

This Resource presents the genetic subset of the 136,000 chemical and genetic perturbations tested by the Joint Undertaking for Morphological Profiling (JUMP) Cell Painting Consortium and associated analysis of phenotypic profiles.

Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). To address this, the authors developed a “Fibrosis Overexpression and Retention (FORT) strategy” that can improve mRNA expression in the fibrotic region and extend the expressed protein in situ.

Antibodies targeting the HIV-1 fusion peptide rarely achieve more than 60% neutralization breadth. Here, the authors develop an anti-FP antibody enhancing its potency to 80% and structurally resolve the expanded FP-binding site that allows the antibody to target diverse viral variants.

The authors show that lipid nanodiscs of different scaffold type and size alter the structure of the pentameric ligand-gated ion channel, ELIC. The results suggest that nanodisc selection is an important consideration for structural studies of membrane proteins.

The underlying charge generation dynamics and structure-property relationships in organic solar cells are not fully understood. Here, the authors demonstrate that interfacial donor-acceptor percolation plays a key role in enabling both high charge generation efficiency and device stability.

In complex oxides, oxygen octahedra are major structural motifs and their tilts sensitively determine the material’s physical properties. Exploiting Coherent Bragg Rod Analysis enables 3D mapping of complex tilt patterns and reveals the means to control polarization through them in CaTiO₃ thin films.

The integration of quantum chemistry and molecular dynamics programs coupled with a graphical user interface provides a streamlined tool for powerful simulations of biomolecular reaction mechanisms.

Target membrane poration is a longstanding enigma in virology. Here, authors show that fusion peptides of the influenza virus’ spike protein aggregate, rotate, and tilt in membranes, facilitating peptide-induced poration during viral fusion.

Here, the authors identify a conformational switch in the amino-terminal transactivation domain of c-MYC, termed coreMYC, which cycles between a closed, inactive state and an open, active conformation. Polyphenol epigallocatechin gallate (EGCG) is used to modulate the conformational landscape of coreMYC, stabilizing the closed and inactive conformation.

Non-addictive treatments for pain are much needed. Here, the authors identify in vivo active leads for inflammatory pain using large library docking against the EP4 prostaglandin receptor.

An integrated approach combing solution and solid-state NMR, molecular dynamics simulations and neutron reflectometry is applied to characterize dynamic membrane bound forms of ADP-ribosylation factor 1 (Arf1).

Despite widespread use of azides across material science and various areas across chemistry, the underlying biosynthetic pathways for its formation have so far been unknown. Now, a promiscuous ATP-utilizing enzyme, Tri17, capable of synthesizing various azide molecules has been identified. Biochemical, structural and computational analyses support a potential molecular mechanism for azide formation by Tri17.

The antidepressant vortioxetine affects rodent and human 5-HT₃ receptors differently. López-Sánchez et al. use a variety of methods, including structure determination of vortioxetine-bound human and mouse 5-HT₃ receptors, to reveal the basis of these differences.

Autotransporter proteins are localised to the bacterial surface and promote colonisation of host epithelial surfaces. Here, the authors present the crystal structure of autotransporter UpaB and show evidence for distinct binding sites for glycosaminoglycans and host fibronectin.

Lipopeptides show great potential as green surfactants but the aggregation behavior of designed lipopeptides bearing linear peptide sequences remains understudied. Here, the authors examine the micellization of chiral lipopeptides bearing lysine-rich tripeptide sequences and investigate structural effects as well as the surface tension and electrical conductivity.

Sodium glucose transporters are critical for maintaining glucose homeostasis. Here, authors provide a detailed framework for how SGLTs utilize cellular membrane potentials to stabilize their substrate accepting conformation leading to accelerated transport.

Multidrug efflux protein pumps are key players in bacterial antimicrobial resistance. Here, the authors show how dynamics of a periplasmic pump component can be targeted for efflux inhibition.

The sorting and assembly machinery (SAM) mediates mitochondrial β-barrel protein folding and membrane insertion. A cryo-EM structure of the yeast SAM complex bound to an early eukaryotic β-barrel intermediate reveals a multipoint guidance mechanism.

Base editors can edit target nucleotides, and identical ones that are within the editing window. Here the authors build an analytical model to propose general principles of editor design to reduce bystander effects.

Asymmetric phospholipid distribution in cell membranes is vital for cellular function. Here, authors reveal how ATP8B1, a P4-ATPase, can transport different lipids, including phosphatidylinositol.

Chunsheng Wang and colleagues develop an electrolyte strategy to enable the use of commercially available microsized alloys, such as Si–Li, as high-performance battery anodes. They ascribe its success to the formation of robust LiF-rich layers as the solid–electrolyte interface.

The local lipid environment is known to affect the structure, stability and intercellular channel activity of gap junctions, however, the molecular basis for these effects remains unknown. Here authors report the CryoEM structure of Cx46/50 lipid-embedded channels, by which they reveal a lipid-induced stabilization to the channel.

Here the authors report a computational approach which integrates deep learning and structural modelling to design target-specific peptides. They apply this to β-catenin and NF-κB essential modulator, resulting in improved binding, highlighting the efficacy of this strategy.

Molecular qubits have great potential as quantum sensors due to their ability to be in close proximity to target analytes, but design guidelines on how to make them respond to specific analytes remain unclear. Here authors show that hybrids of triplet qubits and flexible MOFs can change the coherence time of electron spins of photo-excited triplet state upon adsorption of guest.

The use of energy-dense materials is inherently limited in biphasic self-stratified batteries due to the aqueous electrolyte environment. Here, the authors extended the concept of biphasic self-stratified batteries to non-aqueous systems, resulting in increased energy density and output voltage.

NMDA receptors are glutamate-gated ion channels that regulate fast signaling in the brain. Here, the authors show that the opening and closing patterns of the channel derive from the action of two gates that are regulated by distinct subunits.

Inspired by the design of peptide and nucleic acid sequences to adopt particular three-dimensional shapes, natural glycan motifs have now been combined to construct a glycan that adopts a hairpin conformation in water. Thus a designed glycan can now autonomously fold into a stable secondary structure absent in nature.

It remains challenging to gauge the gas-phase structure of biomolecular ions and assess to what extent native-like structures are maintained. Here, the authors utilize Förster resonance energy transfer and ion mobility spectrometry for more stringent structural characterization of biomolecular ions.

Enteropathogenic bacteria use extracellular appendages, known as F-pili, to share plasmids carrying antibiotic resistance genes. Here, the authors show that F-pili are highly flexible but robust at the same time, and this is important for plasmid transfer and formation of biofilms that protect against the action of antibiotics.

The drug Xanomeline is progressing through clinical trials for the treatment of patients with schizophrenia. Here, the authors determine a cryo-EM structure of Xanomeline bound to its primary target revealing a dual binding mode mechanism.

Albicidin is a peptide antibiotic that has shown great promise for inhibiting DNA topoisomerase of fluoroquinolone-resistant Gram-negative pathogens, but its mode of action is not fully clear. Now, cryoelectron microscopy structures of albicidin–gyrase complexes provide detailed insights into the mechanism of this natural product.

P-type ATPases adopt different conformations during their transport cycle, including autophosphorylated forms. The structure of type IB P-type ATPase CopA is now solved in its E2P state. Comparison with a previous E2Pi structure indicates that dephosphorylation is not coupled to ion extrusion, in contrast to mechanisms in type IIA SERCA. The findings explain the effect of disease-related mutations in human Cu⁺ transporters.

The Legionella collagen-like protein (Lcl) is important for host adhesion in Legionella pneumophila. Here, the authors provide structural and biochemical data, which provides insights into a distinct “fuzzy” glycosaminoglycan binding mechanism.

Stapled α-helical peptides are promising for targeting challenging targets such as transcription factors, but achieving sufficient cell permeability while avoiding off-target cleavage is difficult. Here, the authors present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects based on comprehensive investigations of their properties.

A newly discovered negative allosteric modulator of the µ-opioid receptor works together with naloxone to potently block opioid agonist signalling with reduced adverse effects.

CD59 protects human cells from damage by the MAC immune pore. The authors show how CD59 inhibits MAC, by deflecting pore-forming β-hairpins of complement proteins. As well as how the membrane environment influences the role of CD59 in complement regulation and in host-pathogen interactions.

Mef2D context-dependent higher-order assembly controls simultaneous interactions with the basal machinery and the myogenic factors to activate distinct gene expression programs for muscle lineage development.

Studying rare species in mixtures is challenging. Here, authors utilize on-and-off optical plasmonic trapping to control SERS-active nanocavity to analyse pH-dependent amylin species at single-molecule level, unveiling amyloid aggregation mechanisms.

Isolating the role of water in aqueous reactions where it is directly involved as a reactant is equally important and challenging. Now, by confining water inside an organic liquid matrix, the authors observe the formation of aqueous-rich nanodomains and find that the reactivity of the system varies with their nanostructure.

The direct regioselective oxidation of internal alkenes to ketones poses an important synthetic challenge. Now, directed evolution of a cytochrome P450 enzyme affords a ketone synthase that can efficiently oxidize internal arylalkenes directly to ketones with high chemo- and regioselectivity.