UDP-galactopyranose mutase (UGM) is a flavo-enzyme involved in the bacterial cell wall biosynthesis. UGM catalyzes the reversible isomerization of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf). UDP-Galf is the activated precursor of galactofuranose (Galf) residues that are essential components of the cell wall of certain pathogenic bacteria such as Klebsiella pneumoniae and Mycobacterium tuberculosis. Neither UGM nor Galf residues are found in humans, making Galf biosynthesis a potential drug target for developing antibacterial agents. We report the identification of novel inhibitors of UGM by in silico docking of the LeadQuest compound database against UGM from Escherichia coli. The 13 most promising inhibitors were then evaluated against K. pneumonia and M. tuberculosis UGMs by enzyme inhibition studies. Two inhibitors were identified with IC50 values of ∼1 µM and subsequently these compounds were docked into the recently solved X-ray structure of Deinococcus radiodurans UGM. The structure-activity relationships of the initial 13 compounds evaluated as inhibitors are discussed.
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http://dx.doi.org/10.1002/minf.201100085 | DOI Listing |
Int J Geriatr Psychiatry
January 2025
Precision Neuroscience & Neuromodulation Program, Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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View Article and Find Full Text PDFPilot Feasibility Stud
January 2025
Department of Health Service & Population Research, David Goldberg Centre, King's College London, Denmark Hill, London, UK.
Background: Mental health disorders are one of the leading causes of illness globally. The importance of psychosocial skills acquired in early childhood, such as executive functions, inhibitory control, emotional regulation, and social problem-solving, in preventing mental disorders has been reported. Furthermore, mental health care delivery is evolving, and mobile technology is becoming the medium for assessment and intervention.
View Article and Find Full Text PDFMicrobiome
January 2025
Instituto de Investigación de La Viña y El Vino, Escuela de Ingeniería Agraria, Universidad de León, Avenida de Portugal, 41, León, 24009, Spain.
Background: The main application of cork is the production of stoppers for wine bottles. Cork sometimes contains 2,4,6-trichloroanisole, a compound that, at a concentration of ng/L, produces an unpleasant musty odor that destroys the organoleptic properties of wine and results in enormous economic losses for wineries and cork industries. Cork can exhibit a defect known as yellow stain, which is associated with high levels of 2,4,6-trichloroanisole.
View Article and Find Full Text PDFSci Rep
January 2025
National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry, State Institute of Pharmaceutical Industry, 201203, Shanghai, People's Republic of China.
In Traditional Chinese Medicine (TCM), the medicinal leech is vital for treatments to promote blood circulation and eliminate blood stasis. However, the prevalence of counterfeit leech products in the market undermines the quality and efficacy of these remedies. Traditional DNA barcoding techniques, such as the COI barcode, have been limited in their application due to amplification challenges.
View Article and Find Full Text PDFNPJ Digit Med
January 2025
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Cardiac wall motion abnormalities (WMA) are strong predictors of mortality, but current screening methods using Q waves from electrocardiograms (ECGs) have limited accuracy and vary across racial and ethnic groups. This study aimed to identify novel ECG features using deep learning to enhance WMA detection, referencing echocardiography as the gold standard. We collected ECG and echocardiogram data from 35,210 patients in California and labeled WMA using unstructured language parsing of echocardiographic reports.
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