The VanA D-Ala:D-Lac ligase is a key enzyme in the emergence of high level resistance to vancomycin in Enterococcus species and methicillin-resistant Staphylococcus aureus. It catalyzes the formation of D-Ala-D-Lac instead of the vancomycin target, D-Ala-D-Ala, leading to the production of modified, low vancomycin binding affinity peptidoglycan precursors. Therefore, VanA appears as an attractive target for the design of new antibacterials to overcome resistance. The catalytic site of VanA is delimited by three domains and closed by an ω-loop upon enzymatic reaction. The aim of the present work was (i) to investigate the conformational transition of VanA associated with the opening of its ω-loop and of a part of its central domain and (ii) to relate this transition with the substrate or product binding propensities. Molecular dynamics trajectories of the VanA ligase of Enterococcus faecium with or without a disulfide bridge distant from the catalytic site revealed differences in the catalytic site conformations with a slight opening. Conformations were clustered with an original machine learning method, based on self-organizing maps (SOM), which revealed four distinct conformational basins. Several ligands related to substrates, intermediates, or products were docked to SOM representative conformations with the DOCK 6.5 program. Classification of ligand docking poses, also performed with SOM, clearly distinguished ligand functional classes: substrates, reaction intermediates, and product. This result illustrates the acuity of the SOM classification and supports the quality of the DOCK program poses. The protein-ligand interaction features for the different classes of poses will guide the search and design of novel inhibitors.
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J Neural Transm (Vienna)
January 2025
Institut für Zellbiochemie, OE 4310, Medizinische Hochschule Hannover, 30623, Hannover, Germany.
Botulinum neurotoxins (BoNT) are established biopharmaceuticals for neuromuscular and secretory conditions based on their ability to block neurotransmitter release from neurons by proteolyzing specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, a mutant catalytic domain of serotype E (LC/E) exhibiting 16 mutations was reported to cleave the phosphatase and tensin homolog (PTEN). This molecule represents an attractive new target in neurons as several reports support PTEN knockdown as a strategy to stimulate axonal regeneration after injury.
View Article and Find Full Text PDFAnal Bioanal Chem
January 2025
School of Life Sciences, Nantong University, 9 Seyuan Road, Nantong, 226019, Jiangsu, China.
Hydrogen peroxide (HO) is a critical signaling molecule with significant roles in various physiological processes in plants. Understanding its regulation through in situ monitoring could offer deeper insights into plant responses and stress mechanisms. In this study, we developed a microneedle electrochemical sensor to monitor HO in situ, offering deeper insights into plant stress responses.
View Article and Find Full Text PDFACS Nano
January 2025
College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, P. R. China.
Electrocatalytic CO-to-CO conversion with a high CO Faradaic efficiency (FE) at low overpotentials and industrial-level current densities is highly desirable but a huge challenge over non-noble metal catalysts. Herein, graphitic N-rich porous carbons supporting atomically dispersed nickel (NiN-O sites with an axial oxygen) were synthesized (denoted as O-Ni-N-GC) and applied as the cathode catalyst in a CORR flow cell. O-Ni-N-GC showed excellent selectivity with a FE over 92% at low overpotentials ranging from 17 to 60 mV, and over 99% at 80 mV.
View Article and Find Full Text PDFJ Colloid Interface Sci
January 2025
College of Materials Science and Engineering, Central South University of Forestry and Technology, Changsha 410004 PR China.
Interface engineering and electronic modulation enable precise tuning of the electronic structure, thereby maximizing the efficacy of active sites and significantly enhancing the activity and stability of the electrocatalyst. Herein, a hybrid material composed of Ni-modified CoS nanoparticles ((Co, Ni)S) encapsulated within an N, S co-doped carbon matrix (SNC) and anchored onto S-doped carbonized wood fibers (SCWF) is synthesized using a straightforward simultaneous carbonization and sulfidation approach. Density functional theory (DFT) calculations reveal that the highly electronegative Ni element promotes electron cloud migration from Co to Ni, shifting the d-band center of Co closer to the Fermi level.
View Article and Find Full Text PDFEnviron Sci Technol
January 2025
Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
Pt/CeO single-atom catalysts are attractive materials for CO oxidation but normally show poor activity below 150 °C mainly due to the unicity of the originally symmetric PtO structure. In this work, a highly active and stable Pt/CeO single-site catalyst with only 0.1 wt % Pt loading, achieving a satisfied complete conversion of CO at 150 °C, can be obtained through fabricating asymmetric PtO-oxygen vacancies (O) dual-active sites induced by well-dispersed NbO clusters.
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