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Cluster formation in microscopic swimmers, essential for biofilms and colonies, typically requires high concentrations. Authors show that bent rod shapes, especially semicircles, significantly promote clustering even at low densities, driven by interlocking mechanisms and cluster stability.

Biochemical and structural analysis, combined with metadynamics simulations, illustrate how a single amino acid substitution switches a β-glycosidase from a double S_N2 mechanism to a front-face S_Ni-like mechanism.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) has a crucial role in antigen presentation because it trims peptide ligands to 8–10 residues so that they fit into the peptide-binding groove of MHC class I molecules. The structure of the ERAP1 in complex with bestatin, an aminopeptidase inhibitor, reveals how the enzyme´s catalytic center how the enzyme can preferentially process peptides 10–15 residues long while sparing shorter ones and provides the first evidence that substrate binding induces conformational changes.

Ndeh et al. show that a genetic locus in the human gut bacterium, Bacteroides thetaiotaomicron, encodes a combination of glycosidases, a glycoprotease and a kinase enabling it to process and metabolise O-glycoproteins and the core mucin O-glycan sugar N-acetylgalactosamine.

A diffusion-reaction system in a gel matrix shows that concentration gradients can lead to an overall enhanced catalytic activity.

The endoplasmic-reticulum aminopeptidase ERAP1 processes peptides for antigen presentation. Here, the authors assess ERAP1 conformational states in solution, providing insight into the molecular mechanisms of ERAP1 substrate-length dependent catalytic activity and regulation, including the effects of autoimmune disease-associated polymorphism.

A hydrolytic enzyme with a non-canonical organocatalytic mechanism was generated by introducing N_δ-methylhistidine into a designed active site using engineered translation components, allowing optimization of enzyme performance using laboratory evolution.

The collapse of tropical forests during the Permian–Triassic Mass Extinction weakened carbon sequestration, sustaining high CO2 and extreme global warmth for millions of years: an example of a runaway feedback in Earth’s climate-carbon system.

Antibiotics to treat carbapenem-resistant Acinetobacter baumannii infection are an urgent need. The cerastecins are potent, bactericidal and efficacious in animal models of infection, and may enable new treatment modalities targeting LOS transport.

Enzymes use substrate-binding energy to promote ground-state association and to selectively stabilize the reaction transition state. Mutations in the amino-terminal domain of the monomeric homing endonuclease I-AniI, which cleaves with high sequence specificity in the centre of a 20-base-pair DNA target site, are now found to have different effects on the kinetic parameters of the enzyme than those in the carboxy-terminal domain, revealing an unexpected asymmetry in the use of enzyme–substrate binding energy for catalysis.

A flavin-dependent halogenase with a remarkable preference for iodination has now been discovered. The halogenase (VirX1) was discovered using a bioinformatics-based approach and comes from a cyanophage. Structural characterization and kinetic studies show that VirX1 possesses broad substrate tolerance, making it an attractive tool for synthesis.

Analysis of over 6000 single-site variants of SARS-CoV-2 Papain-Like protease uncovers critical mutations involved in enzymatic function and highlight the potential for drug-escape.

A two-enzyme complex works as a cyclodehydratase to form TOMM natural products, but the roles of each protein have been unclear. Structural and biochemical analysis deconvolutes the roles of each protein and identifies a new ATP-binding motif.

The development of innovative strategies for the capture and biodegradation of nanoplastics is sought after. Now, artificial hydrolytic active sites are incorporated into non-catalytic membrane nanopores generating pore-based biocatalytic nanoreactors that depolymerize polyethylene terephthalate plastic nanoparticles.

NanoLuc luciferase is a popular bioluminescent enzyme, but the molecular details of its mechanism of action on luciferins such as coelenterazine remained elusive. Here the authors use, protein crystal structures and biochemical analyses to provide an atomistic description of its catalytic mechanism and allosteric behaviour.

The authors define a NEDD8-activated cullin-RING E3 poly-ubiquitylation mechanism using chemistry, cryo-EM and rapid kinetics. Near-perfect catalytic efficiency is achieved by an E2 ‘synergy loop’ connecting to the E3, donor and acceptor ubiquitins.

Elastase secreted by immune cells contributes to various lung diseases; however, elastase inhibitors have mostly failed in the clinic. Here, the authors discover a second, truncated form of elastase, which is the result of autocatalytic cleavage and is not well targeted by current synthetic elastase inhibitors.

Aerobic methanotrophic bacteria oxidize methane in sulfide-rich environments, even though hydrogen sulfide (H₂S) inhibits methane oxidation and aerobic respiration. Here, Schmitz et al. show that a single microorganism can oxidize methane and H₂S simultaneously, and this is associated with upregulation of a sulfide-insensitive terminal oxidase.

A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose d-apiose.

Doudna and colleagues determine the mechanisms used by type V anti-CRISPR proteins. AcrVA1 is a multiple-turnover inhibitor that triggers cleavage of the Cas12a-bound guide RNA, while AcrVA4 and AcrVA5 inhibit recognition of dsDNA.

Changing the catalytic metal centre of a non-haem iron dioxygenase to copper results in an enzyme capable of Lewis acid catalysis of new-to-nature enantioselective Conia-ene reactions.

How alcohol-induced plasticity evolves over protracted abstinence is not well understood. Here, authors show the long-lasting impact of drinking on dopamine transmission and that altered function is not explained by upstream gene transcription.

Anticancer drugs such as Taxol can affect microtubule dynamics and organization in cells. Direct visualization of the action of such drugs has shown that they can trigger local and cooperative changes in microtubule lattice and induce formation of stable microtubule regions that promote rescues.

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Here the authors use the evolutionary model EVcouplings to computationally design highly mutated variants of TEM-1 ß-lactamase, and characterise these designs experimentally.

Qiu et al. provide insight into the metabolic adaptations that enable breast cancer cells to proliferate in the face of glutaminolysis blockade.

Celiac disease is characterized by intolerance to gluten, a cereal protein. Here, the authors show that neprosin, a glutamate peptidase from the pitcher plant, efficiently cleaves gluten components under physiological conditions in vitro and in the gut of mice.

The influence of protein motions on the chemical step of enzyme reactions is a contentious issue. Now, by constructing free-energy surfaces using an explicit solvent coordinate, it is shown that, although some structural flexibility is required, protein motions can be described as equilibrium fluctuations.

A pure culture of the complete nitrifier Nitrospira inopinata shows a high affinity for ammonia, low maximum rate of ammonia oxidation, high growth yield compared to canonical nitrifiers and genomic potential for alternative metabolisms, probably reflecting an important role in nitrification in oligotrophic environments.