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Since the emergence of SARS-CoV-2 in 2019, Covid-19 has developed into a serious threat to our health, social and economic systems. Although vaccines have been developed in a tour-de-force and are now increasingly available, repurposing of existing drugs has been less successful. There is a clear need to develop new drugs against SARS-CoV-2 that can also be used against future coronavirus infectio

Steps at metal surfaces may influence energetics and kinetics of catalytic reactions in unexpected ways. Here, we report a significant reduction of the CO saturation coverage in Pd vicinal surfaces, which in turn is relevant for the light-off of the CO oxidation reaction. The study is based on a systematic investigation of CO adsorption on vicinal Pd(111) surfaces making use of a curved Pd crystal

Heparin and heparan sulfate (HS) are linear sulfated disaccharide polymers. Heparin is found mainly in mast cells, while heparan sulfate is found in connective tissue, extracellular matrix and on cell membranes in most tissues. α1-microglobulin (A1M) is a ubiquitous protein with thiol-dependent antioxidant properties, protecting cells and matrix against oxidative damage due to its reductase activi

Purpose:The article makes an empirical and conceptual contribution to understanding the temporalities of information literacies. The paper aims to identify different ways in which anticipation of certain outcomes shapes strategies and tactics for engagement with algorithmic information intermediaries. The paper suggeststhat, given the dominance of predictive algorithms in society, information lite

The one-body density matrix has recently attracted considerable attention as a promising key quantity for the description of systems out of equilibrium. Its time evolution is given in terms of the two-body density matrix, and thus the central challenge is to find approximations to the latter. An extra layer of difficulty is added when dealing with strong electron correlations. In this work, we exp

Poly-ADP-ribose polymerase (PARP)-family ADP-ribosyltransferases function in various signaling pathways, predominantly in the nucleus and cytosol. Although PARP inhibitors are in clinical practice for cancer therapy, the enzymatic activities of individual PARP family members are yet insufficiently understood. We studied PARP10, a mono-ADP-ribosyltransferase and potential drug target. Using acid-ur

Myrosinase from Sinapis alba hydrolyzes glycosidic bonds of β-d-S-glucosides. The enzyme shows an enhanced activity in the presence of l-ascorbic acid. In this work, we employed combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics simulations to study the catalytic reaction of wild-type myrosinase and its E464A, Q187A, and Q187E mutants. Test calculation

Prekallikrein, the precursor to the serine proteinase kailikrein, circulates in plasma in an equimolar complex with H-kininogen. The binding to H-kininogen is mediated by the kallikrein heavy chain consisting of four "apple" domains, A1-A4, which attaches to H-kininogen with high specificity and affinity (KD = 83 UM). At least two distinct portions of the kallikrein heavy chain form this H-kininog

Geosmin is one of the most recognizable and common microbial smells on the planet. Some insects, like mosquitoes, require microbial-rich environments for their progeny, whereas for other insects such microbes may prove dangerous. In the vinegar fly Drosophila melanogaster, geosmin is decoded in a remarkably precise fashion and induces aversion, presumably signaling the presence of harmful microbes

Background: Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Methods: Histology, electron microscopy, bulk and spatial RNA se

Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtob

In recent years, particularly following the definition of the UN Sustainable Development Goals (SDGs) for 2030, Nature-Based Solutions (NBS) have gained considerable attention, capturing the interest of both the scientific community and policymakers committed to addressing urban environmental issues. However, the need for studies to guide decision-makers in identifying suitable locations for NBS i

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

We report results of detailed empirical valence bond simulations that model the effect of several amino acid substitutions on the thermodynamic (ΔG°) and kinetic activation (ΔG⧧) barriers to deprotonation of dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate (GAP) bound to wild-type triosephosphate isomerase (TIM), as well as to the K12G, E97A, E97D, E97Q, K12G/E97A, I170A, L230A,

Human DNA polymerase λ is an intermediate fidelity member of the X family, which plays a role in DNA repair. Recent X-ray diffraction structures of a ternary complex of a loop-deletion mutant of polymerase λ, a deoxyguanosine triphosphate analogue, and a gapped DNA show that guanine and thymine form a mutagenic mispair with an unexpected Watson-Crick-like geometry rather than a wobble geometry. He