Recent years have seen an explosion of interest in understanding the physicochemical parameters that shape enzyme evolution, as well as substantial advances in computational enzyme design. This review discusses three areas where evolutionary information can be used as part of the design process: (i) using ancestral sequence reconstruction (ASR) to generate new starting points for enzyme design eff

Commercial screening services for inheritable diseases raise concerns about pressure on parents to terminate "imperfect babies".

Catalysis by protein tyrosine phosphatases (PTPs) relies on the motion of a flexible protein loop (the WPD-loop) that carries a residue acting as a general acid/base catalyst during the PTP-catalyzed reaction. The orthogonal substitutions of a noncatalytic residue in the WPD-loops of YopH and PTP1B result in shifted pH-rate profiles from an altered kinetic pK a of the nucleophilic cysteine. Compar

DNA-binding proteins play an important role in gene regulation and cellular function. The transcription factors MarA and Rob are two homologous members of the AraC/XylS family that regulate multidrug resistance. They share a common DNA-binding domain, and Rob possesses an additional C-terminal domain that permits binding of low-molecular weight effectors. Both proteins possess two helix-turn-helix

We need more openness about age-related infertility as it is a particular risk for many female scientists in academia who feel that they have to delay having children.

Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern descendants but displays large regions with greatly enhanced conformational flexibility. Yet, the bar

Increasing diversity in academia is not just a matter of fairness but also improves science. It is up to individual scientists and research organisations to support underrepresented minorities.

Bacterial arylmalonate decarboxylase (AMDase) and evolved variants have become a valuable tool with which to access both enantiomers of a broad range of chiral arylaliphatic acids with high optical purity. Yet, the molecular principles responsible for the substrate scope, activity, and selectivity of this enzyme are only poorly understood to date, greatly hampering the predictability and design of

Glycerol-3-phosphate dehydrogenase is a biomedically important enzyme that plays a crucial role in lipid biosynthesis. It is activated by a ligand-gated conformational change that is necessary for the enzyme to reach a catalytically competent conformation capable of efficient transition-state stabilization. While the human form (hlGPDH) has been the subject of extensive structural and biochemical

Mandates with the aim to enforce Open Access publishing, such as Plan S, need to respect researchers' needs and should contribute to the broader goal of Open Science.

Directed evolution has revolutionized protein engineering. Still, enzyme optimization by random library screening remains sluggish, in large part due to futile probing of mutations that are catalytically neutral and/or impair stability and folding. FuncLib is a novel approach which uses phylogenetic analysis and Rosetta design to rank enzyme variants with multiple mutations, on the basis of predic

We uncover the occurrence of shear banding in dense suspensions of compressible microgels. Velocimetry measurements evidence the presence of permanent but unsteady shear-banding for sufficiently small Peclet numbers, with the formation of a central plug-like flow. Small-angle neutron scattering experiments under shear link the observed banding phenomenon to structural variations along the velocity

We consider the most energetically favorable symmetry-allowed spin-singlet and spin-triplet superconducting pairing symmetries in twisted bilayer graphene at the magic angle, whose normal state physics is described by a six-band effective tight-binding model. We compute the Chern number as a function of the superconducting order parameter strength and the chemical potential and we find a topologic

Background: Calcineurin inhibitors (CNIs) are associated with long-term complications after heart transplantation (HTx). Everolimus (EVR)-based immunosuppression allows for CNI withdrawal. We used data from The Scandinavian heart transplant everolimus de novo study with early CNI avoidance (SCHEDULE) trial to assess whether health-related quality of life (HRQoL) differed between patients on long-t

In recent years, remote sensing data have revealed considerable potential in unraveling crucial information regarding water balance dynamics due to their unique spatiotemporal distribution characteristics, thereby advancing multi-objective optimization algorithms in hydrological model parameter calibration. However, existing optimization frameworks based on the Soil and Water Assessment Tool (SWAT

In this work, we present results of numerical simulations of the formation and early evolution of rocky planets through pebble accretion, with an emphasis on hydrogen envelope longevity and the composition of the outgassed atmosphere. We modelled planets with a range in mass from 0.1 to 5 Earth masses that orbit between 0.7 and 1.7 AU. The composition of the outgassed atmosphere was calculated wit

Background: SepIVA has been reported to be an essential septation factor in Mycolicibacterium smegmatis and Mycobacterium tuberculosis. It is a coiled-coil protein with similarity to DivIVA, a protein necessary for polar growth in members of the phylum Actinomycetota. Orthologues of SepIVA are broadly distributed among actinomycetes, including in Streptomyces spp. Results: To clarify the role of S

Context. The Gaia-Sausage-Enceladus merger was a major event in the history of the Milky Way. Debris from this merger has been extensively studied with full kinematic data from the Gaia mission. Understanding the star formation history of the progenitor galaxy aids in our understanding of the evolution of the Milky Way and galaxy formation in general. Aims. We aimed to constrain the star formation

Background and aim: The popularity of remote and blended teachings in physiotherapy higher education is increasing. Initial evidence suggests that these methods are as effective as face-to-face teaching for theoretical and practical skill learning in physiotherapy; however, further research is required. Methods: This was a retrospective comparative study. Three groups of physiotherapy students und