A5005416775- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Cancer, Hypoxia, and Metabolism
- Metal-Catalyzed Oxygenation Mechanisms
- Microbial metabolism and enzyme function
- Carcinogens and Genotoxicity Assessment
- Microbial bioremediation and biosurfactants
- Cholinesterase and Neurodegenerative Diseases
- Radioactive element chemistry and processing
- Folate and B Vitamins Research
- Pneumonia and Respiratory Infections
- Neurogenesis and neuroplasticity mechanisms
- Tuberculosis Research and Epidemiology
- Hemoglobin structure and function
- Glioma Diagnosis and Treatment
- Porphyrin and Phthalocyanine Chemistry
- Luminescence and Fluorescent Materials
- Pneumocystis jirovecii pneumonia detection and treatment
- Enzyme Structure and Function
- Biochemical effects in animals
- Endoplasmic Reticulum Stress and Disease
- Pesticide Exposure and Toxicity
- Chemical Reactions and Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Analytical Methods in Pharmaceuticals
University of Oxford
2014-2021
Oxford Research Group
2020
Science Oxford
2014
Humboldt-Universität zu Berlin
2008
Abstract The New Delhi metallo‐β‐lactamase (NDM‐1) is involved in the emerging antibiotic resistance problem. Development of metallo‐β‐lactamases (MBLs) inhibitors has proven challenging, due to their conformational flexibility. Here we report site‐selective labeling NDM‐1 with 1,1,1‐trifluoro‐3‐bromo acetone (BFA), and its use study binding events changes upon ligand–metal using 19 F NMR spectroscopy. results demonstrate different modes known inhibitors, including L ‐ D ‐captopril by...
ObjectivesMetallo-β-lactamase (MBL)-based resistance is a threat to the use of most β-lactam antibiotics. Multiple variants New Delhi MBL (NDM) have recently been reported. Previous reports indicate that substitutions affect NDM activity despite being located outside active site. This study compares biochemical properties seven clinically reported variants.
Abstract AspH is an endoplasmic reticulum (ER) membrane-anchored 2-oxoglutarate oxygenase whose C-terminal and tetratricopeptide repeat (TPR) domains present in the ER lumen. catalyses hydroxylation of asparaginyl- aspartyl-residues epidermal growth factor-like (EGFDs). Here we report crystal structures human AspH, with without substrate, that reveal substantial conformational changes TPR during substrate binding. Fe(II)-binding by unusual, employing only two ligands (His679/His725). Most...
Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibiotics. We report biophysical and kinetic studies on São Paulo MBL (SPM-1), which reveal its Zn(ii) ion usage mechanism as characteristic clinically important di-Zn(ii) dependent B1 subfamily. Biophysical analyses employing crystallography, dynamic
Abstract The human 2-oxoglutarate dependent oxygenase aspartate/asparagine-β-hydroxylase (AspH) catalyses the hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs). AspH is upregulated on surface malign cancer cells; increased levels correlate with tumour invasiveness. Due to a lack efficient assays monitor activity isolated AspH, there are few reports studies aimed at identifying small-molecule inhibitors. Recently, it was reported that substrates have...
Abstract Resistance to β‐lactam antibiotics mediated by metallo‐β‐lactamases (MBLs) is a growing problem. We describe the use of protein‐observe 19 F‐NMR (PrOF NMR) study dynamics São Paulo MBL (SPM‐1) from β‐lactam‐resistant Pseudomonas aeruginosa . Cysteinyl variants on α3 and L3 regions, which flank di‐Zn II active site, were selectively F‐labeled using 3‐bromo‐1,1,1‐trifluoroacetone. The PrOF NMR results reveal roles for mobile regions in binding both inhibitors hydrolyzed products...
Abstract Aspartate/asparagine‐β‐hydroxylase (AspH) is a human 2‐oxoglutarate (2OG) and Fe II oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues epidermal growth factor‐like domains (EGFDs). Unusually, AspH employs two histidine to chelate rather than the typical triad one glutamate/aspartate residue. We report kinetic, inhibition, crystallographic studies concerning variants in which either its binding are substituted for alanine. Both H725A and, particular, H679A...
The spectral evolution of fluorescence from 4-(dimethylamino)-4'-cyanostilbene (DCS) in methanol, and two derivatives bearing either the anilino (ACS) or julolidino (JCS) moiety, was measured by optical Kerr-gating with a time resolution 0.35 ps. A special thin Glan polariser Kerr shutter allows high contrast without unnecessarily increasing group delay dispersion. emission band may thus be gated observed even highly fluorescent samples. dynamics consists continuous red-shift narrowing...
Abstract The New Delhi metallo‐β‐lactamase (NDM‐1) is involved in the emerging antibiotic resistance problem. Development of metallo‐β‐lactamases (MBLs) inhibitors has proven challenging, due to their conformational flexibility. Here we report site‐selective labeling NDM‐1 with 1,1,1‐trifluoro‐3‐bromo acetone (BFA), and its use study binding events changes upon ligand–metal using 19 F NMR spectroscopy. results demonstrate different modes known inhibitors, including L ‐ D ‐captopril by...
Abstract Resistance to β‐lactam antibiotics mediated by metallo‐β‐lactamases (MBLs) is a growing problem. We describe the use of protein‐observe 19 F‐NMR (PrOF NMR) study dynamics São Paulo MBL (SPM‐1) from β‐lactam‐resistant Pseudomonas aeruginosa . Cysteinyl variants on α3 and L3 regions, which flank di‐Zn II active site, were selectively F‐labeled using 3‐bromo‐1,1,1‐trifluoroacetone. The PrOF NMR results reveal roles for mobile regions in binding both inhibitors hydrolyzed products...
Antibiotikaresistenz ist ein weltweites Gesundheitsproblem. Metallo-β-lactamasen katalysieren die Hydrolyse von nahezu allen β-Lactam-Antibiotika. T. D. W. Claridge, C. J. Schofield et al. zeigen in ihrer Zuschrift auf S. 3193 ff., wie 19F-NMR-Spektroskopie genutzt werden kann, um Bindungsweise Inhibitoren der New-Delhi-Metallo-β-lactamase I (NDM-1) zu untersuchen: Man markiert eine Schleife im aktiven Zentrum mit 19F und kann dann Änderungen lokalen chemischen Umgebung, durch Bindung des...
Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and Fe
An amendment to this paper has been published and can be accessed via a link at the top of paper.