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Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation

ATP phosphoribosyltransferase catalyses the first step of histidine biosynthesis and is controlled via a complex allosteric mechanism where the regulatory protein HisZ enhances catalysis by the catalytic protein HisGS while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisGS Arg56 to stabilise departure of the pyrophosphate leaving group. Here we report

The evolution of multiple active site configurations in a designed enzyme

Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we fo

Shuffling Active Site Substate Populations Affects Catalytic Activity : The Case of Glucose Oxidase

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

Investigating the differences in calculating global mean surface CO2 abundance: the impact of analysis methodologies and site selection

The World Meteorological Organization (WMO) Global Atmosphere Watch (GAW) coordinates high-quality atmospheric greenhouse gas observations globally and provides these observations through the WMO World Data Centre for Greenhouse Gases (WDCGG) supported by Japan Meteorological Agency. The WDCGG and the National Oceanic and Atmospheric Administration (NOAA) analyse these measurements using different

Similar Active Sites and Mechanisms Do Not Lead to Cross-Promiscuity in Organophosphate Hydrolysis : Implications for Biotherapeutic Engineering

Organophosphate hydrolases are proficient catalysts of the breakdown of neurotoxic organophosphates and have great potential as both biotherapeutics for treating acute organophosphate toxicity and as bioremediation agents. However, proficient organophosphatases such as serum paraoxonase 1 (PON1) and the organophosphate-hydrolyzing lactonase SsoPox are unable to hydrolyze bulkyorganophosphates with

Computational Study of the pKa Values of Potential Catalytic Residues in the Active Site of Monoamine Oxidase B

Monoamine oxidase (MAO), which exists in two isozymic forms, MAO A and MAO B, is an important flavoenzyme responsible for the metabolism of amine neurotransmitters such as dopamine, serotonin, and norepinephrine. Despite extensive research effort, neither the catalytic nor the inhibition mechanisms of MAO have been completely understood. There has also been dispute with regard to the protonation s

Site localisation on bacterial surface proteins using super resolution imaging

I snart 500 år har människan använt sig av diverse optiska instrument för att betrakta sådant som inte är möjligt att se med blotta ögat. Teleskop har använts för att studera himlakroppar och mikroskop för att exempelvis undersöka små biologiska beståndsdelar. Det finns idag många olika metoder inom optisk mikroskopi men samtliga följer en liknande grundprincip. Objektet som ska avbildas exponerasSeveral significant pathogenic bacteria exhibit surface proteins that bind human antibodies, preventing them from being recognized by the human immune system. These bacteria are thus protected from elimination and can survive in the host organism. One common such bacteria is the Streptococcus pyogenes that exhibits the antibody binding M protein on its surface. Streptococcus pyogenes causes more t

Values shaping consumer interactions on social commerce sites within game retail

The game industry has continued to grow for decades and the social interaction trend has been growing for years in gaming. In retail, the e-commerce companies have been extending the social interaction trend to the e-commerce platforms and turning the e-commerce into social commerce. Even though the social commerce and gaming have aroused the interest of the researchers earlier, social commerce in

Regulation of HPV16 splice sites located in the E6/E7 oncogene coding region

Kan cellers proteiner bota HPV- sjukdomar? Livmoderhalscancer är en av de vanligaste cancersjukdomarna som drabbar kvinnor världen över. Varje år, diagnostiseras ungefär 500 000 kvinnor och 270 000 dör i sjukdomen, varav de flesta dödsfallen sker i utvecklingsländer. Livmoderhalscancer orsakas av det vanligt förekommande viruset humant papillomvirus (HPV) och för att hitta bättre behandling mot sHuman papillomaviruses (HPVs) are small DNA viruses that have evolved over millions of years and are well-adapted to humans. Persistent infections with HPVs, can result in cancer development. There are over 200 different HPV types that can be divided into high- and low risk types based on their ability to cause cancer. HPV16 is the most common high- risk type that accounts for more than 50 % of al

Cultural Heritage, Our Shared Legacy: A Study of Value Co-Creation in Archaeological Site Management

Cultural tourism and cultural heritage management, while distinct disciplines with differing foci, are also inherently intertwined. However, conflicts between the two often arise due to the diverse number of stakeholders and interests involved in either the travel industry or the conservation and protection of cultural heritage. Despite this, cultural tourism can greatly benefit the conservation o