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Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with ph

GTP Hydrolysis Without an Active Site Base : A Unifying Mechanism for Ras and Related GTPases

GTP hydrolysis is a biologically crucial reaction, being involved in regulating almost all cellular processes. As a result, the enzymes that catalyze this reaction are among the most important drug targets. Despite their vital importance and decades of substantial research effort, the fundamental mechanism of enzyme-catalyzed GTP hydrolysis by GTPases remains highly controversial. Specifically, ho

Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1

Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, co

Influence of nuclides and chelators on imaging using affibody molecules : comparative evaluation of recombinant affibody molecules site-specifically labeled with ⁶⁸Ga and ¹¹¹In via maleimido derivatives of DOTA and NODAGA

Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use of the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity of HER2 imaging. The chemical nature of radionuclides and chelators

Effects of conventionally treated and ozonated wastewater on the damselfly larva oxylipidome in response to on-site exposure

Pharmaceutical residues discharged through insufficiently treated or untreated wastewater enter aquatic environments, where they may adversely impact organisms such as aquatic invertebrates. Ozonation, an advanced wastewater treatment technique, has been successfully implemented to enhance the removal of a broad range of pharmaceuticals, however diverse byproducts and transformation products that

The ethics and politics of world heritage : local application at the site of Laponia

This article explores the ethics of world heritage (WH) through a cosmopolitan lens. It proposes that cosmopolitanism provides fertile ground for the study of WH, in particular if combined with sensitivity to distinct indigenous ethical and political claims. Underpinning my article is the question of whether the politics of WH, despite its peaceful and universalist intensions, obscures local dispu

Conformational Response of 30S-bound IF3 to A-Site Binders Streptomycin and Kanamycin

Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangemen

Novel Function of CtXyn5A from Acetivibrio thermocellus: Dual Arabinoxylanase and Feruloyl Esterase Activity Occur in the Same Active Site

Uncharacterized side activities of enzymes can have significant negative effects on reaction products and yields. Hence, their identification and characterization is crucial for the development of successful reaction systems. Here, we report the presence of feruloyl esterase activity in CtXyn5A from Acetivibrio thermocellus besides its well-known arabinoxylanase activity for the first time. Both r

Translational stalling at polyproline stretches is modulated by the sequence context upstream of the stall site

The polymerization of amino acids into proteins occurs on ribosomes, with the rate influenced by the amino acids being polymerized. The imino acid proline is a poor donor and acceptor for peptide-bond formation, such that translational stalling occurs when three or more consecutive prolines (PPP) are encountered by the ribosome. In bacteria, stalling at PPP motifs is rescued by the elongation fact

Multimodal ex vivo methods reveal that Gd-rich corrosion byproducts remain at the implant site of biodegradable Mg-Gd screws

Extensive research is being conducted on magnesium (Mg) alloys for bone implant manufacturing, due to their biocompatibility, biodegradability and mechanical properties. Gadolinium (Gd) is among the most promising alloying elements for property control in Mg alloy implants; however, its toxicity is controversial. Investigating Gd behavior during implant corrosion is thus of utmost importance. In t

Putative ligand binding sites of two functionally characterized bark beetle odorant receptors

Background: Bark beetles are major pests of conifer forests, and their behavior is primarily mediated via olfaction. Targeting the odorant receptors (ORs) may thus provide avenues towards improved pest control. Such an approach requires information on the function of ORs and their interactions with ligands, which is also essential for understanding the functional evolution of these receptors. Henc

Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function

TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore how TRPV2 activity is modulated by the phytocannabinoid Δ9-tetrahydrocannabiorcol (C16) and by probenecid. C16 and probenecid act in concert to stimulate TRPV2 responses including histamine release from

Smoking increases donor site complications in breast reconstruction with DIEP flap

Objective: Reconstruction with deep inferior epigastric perforator flap (DIEP) is considered to be the first choice for autologous breast reconstruction. The primary aims of this retrospective study were to find out if differences in smoking habits and BMI are useful predictors for postoperative complications in DIEP surgery. Methods: Three hundred and one patients were included. Data regarding sm

Adsorption-site determination of ordered Yb on Si(111) surfaces

Low-energy-electron-diffraction (LEED), scanning-tunneling-microscopy (STM), and photoelectron-spectroscopy measurements have been performed on the ordered submonolayer surface reconstructions of Yb on Si(111). Two of these reconstructions, namely, 3×1 and 2×1, have been studied in detail. STM and LEED revealed that what was considered to be the 3×1 reconstruction is actually a 3×2 reconstruction.

Where are the missing boatyards? Steaming pits as boat building sites in the Nordic Bronze Age

Abstract in GermanDas Boot gilt als ein herausragendesSymbol der nordischen Bronzezeit, dargestellt in Tausendenvon Felsbildern und auf vielen Metallgegenständen in ganzSkandinavien. Paradoxerweise sind direkte Hinweise aufdiese Boote rar, und die Orte, an denen Boote gebaut wurden,bleiben größtenteils schwer fassbar. In diesem Artikel schla-gen wir vor, dass die sogenannten Kochgruben entlang der