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Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-of-the-art computational and experimental
The recruitment and evolutionary optimization of promiscuous enzymes is key to the rapid adaptation of organisms to changing environments. Our understanding of the precise mechanisms underlying enzyme repurposing is, however, limited: What are the active-site features that enable the molecular recognition of multiple substrates with contrasting catalytic requirements? To gain insights into the mol
The epoxide hydrolase StEH1 catalyzes the hydrolysis of trans-methylstyrene oxide to 1-phenyl-propane-1,2-diol. The (S,S)-epoxide is exclusively transformed into the (1R,2S)-diol, while hydrolysis of the (R,R)-epoxide results in a mixture of product enantiomers. In order to understand the differences in the stereoconfigurations of the products, the reactions were studied kinetically during both th
The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of C
Researchers using eye tracking are heavily dependent on software and hardware tools to perform their studies, from recording eye tracking data and visualizing it, to processing and analyzing it. This article provides an overview of available tools for research using eye trackers and discusses considerations to make when choosing which tools to adopt for one's study.
Characterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), an organophosphate-degrading enzyme. We ident
The amphiphilic nature of the amyloid-β (Aβ) peptide associated with Alzheimer's disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of Aβ(1-40) in the presence of surfactants with varying physicochemica
We have previously performed empirical valence bond calculations of the kinetic activation barriers, Δ G‡calc, for the deprotonation of complexes between TIM and the whole substrate glyceraldehyde-3-phosphate (GAP, Kulkarni et al. J. Am. Chem. Soc. 2017 , 139 , 10514 - 10525 ). We now extend this work to also study the deprotonation of the substrate pieces glycolaldehyde (GA) and GA·HPi [HPi = pho
β-Phosphoglucomutase (β-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of β-glucose-1-phosphate to β-glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mechanism is that both steps are concerted processes involving acid-base catalysis from a nearby
Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enz
Glucose oxidase has wide applications in the pharmaceutical, chemical, and food industries. Many recent studies have enhanced key properties of this enzyme using directed evolution, yet without being able to reveal why these mutations are actually beneficial. This work presents a synergistic combination of experimental and computational methods, indicating how mutations, even when distant from the
Enzymes are flexible catalysts, and there has been substantial discussion about the extent to which this flexibility contributes to their catalytic efficiency. What has been significantly less discussed is the extent to which this flexibility contributes to their evolvability. Despite this, recent years have seen an increasing number of both experimental and computational studies that demonstrate
Dams are vital for irrigation, power generation, and domestic water needs, but siltation poses a significant challenge, especially in areas prone to water erosion, potentially shortening a dam’s lifespan. The Ahmed El Hansali Dam in Morocco faces heightened siltation due to its upstream region being susceptible to erosion-prone rocks and high runoff. This study estimates the siltation at the dam f
Clustering samples based on similarity remains a significant challenge, especially when the goal is to accurately capture the underlying data clusters of complex arbitrary shapes. Existing density-based clustering techniques are known to be best suited for capturing arbitrarily shaped clusters. However, a key limitation of these methods is the difficulty in automatically finding the optimal set of
Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and harms of methylxanthines in preventing or treating intermittent hypoxemia or respiratory insufficiency in late preterm infants.
Clinical genetic laboratories often require a comprehensive analysis of chromosomal rearrangements/structural variants (SVs), from large events like translocations and inversions to supernumerary ring/marker chromosomes and small deletions or duplications. Understanding the complexity of these events and their clinical consequences requires pinpointing breakpoint junctions and resolving the deriva
Knock detection is critical for maintaining engine performance and preventing damage in spark-ignition engines. This study explores the use of ion current and knock indicators derived from a vibration sensor ((Formula presented.)) and ion current ((Formula presented.)) to improve knock detection accuracy. Traditional threshold-based methods rely on (Formula presented.), but they are susceptible to
För en utförlig populärvetenskaplig sammanfattning, vänligen följ länken till höger på denna sidan. De svenska utbildningsmyndigheterna står inför ett seglivat problem. Lärare har under många år uttryckt missnöje över alltmer utbredda och genomgripande krav på dokumentation. En hel del dokumentation stjäl tid som annars skulle kunna läggas på elevers lärande och att utveckla undervisningen, lyder The Swedish education authorities are up against a tenacious problem. Teachers have for years expressed dissatisfaction over increasingly prolific and pervasive demands for documentation that hijacks time that could have been invested in pupils’ learning. Over the past 15 years different Swedish governments have sought to remedy this problem but to no avail. The ‘burden of documentation’, as it is
Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 in 6-h intervals and combined this new dataset with our previous atlas (E6.5-E8.5) to produce a densely sampled timecourse of >400,000 cells from early gastrulation to orga
In 1926, the Finnish physician Erik Adolf von Willebrand first described an inherited bleeding disorder with features that suggested that this disease was distinct from classic hemophilia and other bleeding disorders. The original observations were made by members of a large family (family S) living on the island of Föglö in the Åland archipelago in the Baltic Sea. The index case was a young girl,
