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RNF213 is an E3 ligase with ATPase activity. Here, the authors show that RNF213 is activated by ATP binding and senses cellular energy states, and reveal a transthiolation mechanism induced by immune signals through ATP increase in macrophages.

Continued deoxygenation of the oceans will probably lead to enhanced demand for iron, as implied by the abundance of an iron-rich enzyme in the mesopelagic waters of the Pacific.

Heat capacity changes affect the temperature dependence of enzyme catalysis, with implications for thermoadaptation, however their physical basis is unknown. Here the authors show that heat capacity changes are calculable by simulation, revealing distinct dynamical contributions from regions remote from the active site.

A β-lactamase, a novel type of amidase, and the phenylacetic acid catabolon comprise a catabolic pathway, revealed by genomic and transcriptomic analysis, that enables multiple soil bacteria to use β-lactam antibiotics as a carbon source.

The SIT1-ACE2 complex transports the amino acid proline and is the receptor of SARS-CoV-2. Here, the authors identify specific sequence requirements for proline transport and explain for how a missense mutation causes iminoglycinuria.

The development of direct-acting antivirals to combat COVID-19 remains an important goal. Here the authors design covalent inhibitors that target the papain-like protease from SARS-CoV-2. The most promising inhibitor blocks viral replication in mammalian cells.

Directed evolution of a primitive computationally designed enzyme has produced an efficient and enantioselective biocatalyst for the Morita–Baylis–Hillman reaction. The engineered enzyme uses a designed histidine nucleophile operating in synergy with a catalytic arginine that emerged during evolution and serves as a genetically encoded surrogate of privileged bidentate hydrogen-bonding catalysts.

Enzyme promiscuity seeds evolutionary innovation, but how flexible a single enzyme can be (re-)used during evolution remains unclear. Here, the authors show that various evolutionary trajectories applied to succinate semialdehyde dehydrogenase can compensate for the loss of two different functions in E. coli.

Rpn11, the only essential deubiquitinase (DUB) of the 26S proteasome, sits at the top of the substrate entry pathway and facilitates substrate degradation through cotranslocational deubiquitination. The structure of the Rpn11–Rpn8 complex, together with functional assays, offers insight into Rpn11's promiscuous DUB activity during proteasomal degradation.

Cryo-EM illuminates atomic binding details and far-ranging conformational effects of the inhibitor targocil-II on wall teichoic acid ABC transporter TarGH, a virulence target from the antibiotic resistant, often hospital acquired pathogen S. aureus.

Generation and iterative optimization of designed enzymes can provide valuable insights for a more efficient catalysis. Here the authors have followed the iterative improvement of a designed Kemp eliminase and show that remote point mutations could remodel the designed active site via substantial conformational reorganization.

The plasma metalloprotease ADAMTS13 regulates the platelet-tethering function of von Willebrand factor (VWF) in a shear-dependent manner. Here the authors present the ADAMTS13 crystal structure of the 70kDa N-terminal metalloprotease to spacer domains, and using kinetic measurements they identify a substrate binding induced allosteric mechanism for ADAMTS13, where VWF functions both as an activating cofactor and substrate.

Cofactor F₄₂₀ plays crucial roles in bacterial and archaeal metabolism, but its biosynthetic pathway is not fully understood. Here, the authors present the structure of one of the enzymes and provide experimental evidence for a substantial revision of the pathway, including the identification of a new intermediate.

Mucins are glycosylated proteins with important biological functions such as protection. Although glycopeptidases can cleave them, dedicated hydrolytic enzymes specific for mucins were unknown. Now microbial mucinases are discovered that specifically recognize mucin O-glycan clusters and employ two glutamic acid residues for catalytic cleavage.

Wang et al. report a structure for human MBOAT7, the enzyme responsible for remodeling acyl chains of phosphatidylinositol. The structure enabled the identification of MBOAT7 inhibitors and provides insights into substrate specificity among MBOATs.

Ribonuclease P efficiently processes all tRNA precursors despite sequence variation at the site of cleavage. Here, authors use high-throughput enzymology and cryoEM to reveal conformational changes that drive recognition by bacterial RNase P.

The Lon protease is an important protein degradation machine and is conserved across the three domains of life. Here, the authors describe a small proteotoxic stress-induced protein that functions as an allosteric activator of Lon.

Receptor-linked protein tyrosine phosphatases (RPTPs) usually contain an active membrane proximal domain and an inactive pseudophosphatase domain. Here, the authors characterize an RPTP with two pseudophosphatase domains, providing evidence that it may act as a decoy receptor for substrate sequestration.

Simple enzyme mimetics are highly desired for industrial settings providing high catalyst stability and low production costs. This work reports that phenylalanine and zinc ions can self-assemble into a supramolecular structure showing catalytic properties similar to those of the natural enzyme carbonic anhydrase.

Glutamine synthetase is the only enzyme that synthesizes glutamine in mammals. In vivo metabolomics showed that glutamine synthetase utilizes methylamine to produce N⁵-methylglutamine, whose levels correlate with tumor burden in a β+catenin+mutant liver cancer model.

Here, the authors describe a tubular module connecting oxidoreductases to the membrane. This system, found in many microorganisms, reveals a distinct mode of membrane anchoring and an electron transfer mechanism involved in energy conservation.

An optimized nanosensor with tumour-penetrating ligands and with peptide substrates that lead to maximal tumour-specific protease cleavage detects sub-5 mm lesions in human epithelial tumour xenografts and in an orthotopic model of ovarian cancer.

A family of regulators named Catalytic Core Regulators (CCRs) oversees the function of the 20S proteasome. Here, the authors show that CCRs function through an allosteric mechanism, coupling the physical binding of the PSMB4 β-subunit with attenuation of the proteasome three proteolytic activities.

Acetyl-CoA assimilation pathways are usually associated with the loss of carbon in the form of CO₂. Here, the authors report a new metabolic pathway enabled by an engineered B₁₂-dependent acyl-CoA mutase, in which CO₂ is fixed during acetyl-CoA assimilation.

A Toxoplasma gondii mucin-type O-glycosyltransferase uses a unique catalytic mechanism to modify bradyzoite cyst wall proteins. A second metal coupled to substrate binding is required for catalysis, while an active site glutamate suggests a double-displacement mechanism.

Ancestral protein reconstruction followed by biochemical and structural analyses characterizes the evolutionary trajectory of methyl-parathion hydrolase from an ancestral dihydrocoumarin hydrolase through the accumulation of five key mutations.

Metagenomic analysis has uncovered a previously uncharacterized clade of Rubisco related to form I Rubisco found in plants and cyanobacteria. Structural and kinetic data show how this proto-form I Rubisco assembles and functions without small subunits.

Auxin regulates multiple aspects of plant growth and development. Here Dindas et al. show that in root-hair cells, the AUX1 auxin influx carrier mediates proton-driven auxin import that is perceived by auxin receptors and coupled to Ca²⁺ waves that may modulate adaptive responses in the root.

Computationally designed enzymes often show lower activity or stability than their natural counterparts. Here, the authors present an evolution-inspired method for automated enzyme design, creating stable enzymes with accurate active site architectures and wild-type-like activities.

Ammonia oxidation is carried out by both Bacteria and Archaea. Oligotrophic ammonia oxidation kinetics and cellular characteristics of a mesophilic crenarchaeon found in the open ocean are now reported; its remarkably high specific affinity for reduced nitrogen suggests that certain ammonia-oxidizing Archaea could successfully compete with heterotrophic bacterioplankton and phytoplankton. Thus, ammonia oxidation may be more prevalent in the marine nitrogen cycle than is currently accounted for.