Effects of altering the properties of an active site in an enzymatic homogeneous catalyst have been extensively reported. However, the possibility of increasing the number of such sites, as commonly done in heterogeneous catalytic materials, remains unexplored, particularly because those have to accommodate appropriate residues in specific configurations. This possibility was investigated by using a serine ester hydrolase as the target enzyme. By using the Protein Energy Landscape Exploration software, which maps ligand diffusion and binding, we found a potential binding pocket capable of holding an extra catalytic triad and oxyanion hole contacts. By introducing two mutations, this binding pocket became a catalytic site. Its substrate specificity, substrate preference, and catalytic activity were different from those of the native site of the wild type ester hydrolase and other hydrolases, due to the differences in the active site architecture. Converting the binding pocket into an extra catalytic active site was proven to be a successful approach to create a serine ester hydrolase with two functional reactive groups. Our results illustrate the accuracy and predictive nature of modern modeling techniques, opening novel catalytic opportunities coming from the presence of different catalytic environments in single enzymes.
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http://dx.doi.org/10.1021/acs.biochem.8b00274 | DOI Listing |
Food Sci Nutr
January 2025
Modern-day consumers are interested in highly nutritious and safe foods with corresponding organoleptic qualities. Such foods are increasingly subjected to various processing techniques which include the use of enzymes. These enzymes like amylases, lipases, proteases, xylanases, laccases, pullulanase, chitinases, pectinases, esterases, isomerases, and dehydrogenases could be derived from extremophilic organisms such as thermophiles, psychrophiles, acidophiles, alkaliphiles, and halophiles.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
Introduction: Acute respiratory distress syndrome (ARDS) is a life-threatening type of acute lung injury (ALI) characterized by elevated mortality rates and long-term effects. To date, no pharmacological treatment has proven effective for ARDS. Mesenchymal stem cell-derived apoptotic vesicles (apoVs) were recently found to have excellent therapeutic potential for inflammatory diseases.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, Novosibirsk, Russian Federation.
Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated.
View Article and Find Full Text PDFRen Fail
December 2025
Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Background: Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) have an unparalleled risk of vascular calcification (VC) and high alkaline phosphatase (Alk-P) levels. However, whether VC contributed to the cardiovascular risk modified by serum Alk-P levels was not addressed in the population.
Methods: A retrospective cohort study was conducted on chronic HD patients, between October 1 and December 31, 2018, with aortic arch calcification (AoAC) scores and serum Alk-P levels.
JMIR Form Res
January 2025
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Medical Sciences Building II, Room 4741, Ann Arbor, MI, 48109, United States, 1 734-647-2964.
Background: Insulin resistance and the G allele of rs738409 interact to create a greater risk of metabolic dysfunction-associated steatotic liver disease.
Objective: This study aims to confirm that one promising way to reduce insulin resistance is by following a very low-carbohydrate (VLC) dietary pattern.
Methods: Adults with rs738409-GG or -CG with liver steatosis and elevated liver function tests, were taught an ad libitum VLC diet, positive affect and mindful eating skills, goal setting, and self-monitoring and given feedback and coaching for 4 months.
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