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Co-assembling enzymes with nanoparticles (NPs) into nanoclusters allows them to access channeling, a highly efficient form of multienzyme catalysis. Using pyruvate kinase (PykA) and lactate dehydrogenase (LDH) to convert phosphoenolpyruvic acid to lactic acid with semiconductor quantum dots (QDs) confirms how enzyme cluster formation dictates the rate of coupled catalytic flux (k) across a series of differentially sized/shaped QDs and 2D nanoplatelets (NPLs). Enzyme kinetics and coupled flux were used to demonstrate that by mixing different NP systems into clusters, a >10× improvement in k is observed relative to free enzymes, which is also ≥2× greater than enhancement on individual NPs. Cluster formation was characterized with gel electrophoresis and transmission electron microscopy (TEM) imaging. The generalizability of this mixed-NP approach to improving flux is confirmed by application to a seven-enzyme system. This represents a powerful approach for accessing channeling with almost any choice of enzymes constituting a multienzyme cascade.
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http://dx.doi.org/10.1016/j.crmeth.2024.100764 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.
Multivalent binding and the resulting dynamical clustering of receptors and ligands are known to be key features in biological interactions. For optimizing biomaterials capable of similar dynamical features, it is essential to understand the first step of these interactions, namely the multivalent molecular recognition between ligands and cell receptors. Here, we present the reciprocal cooperation between dynamic ligands in supramolecular polymers and dynamic receptors in model cell membranes, determining molecular recognition and multivalent binding via receptor clustering.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Background: Antimicrobial resistance is a globally recognised public health threat. In rural China, antibiotic use is common for acute respiratory infections (ARIs), which include symptoms such as coughing and fever that are most likely viral infections but with a small proportion as bacterial infections. This study aims to evaluate the effectiveness of a comprehensive intervention based on C-reactive protein and serum amyloid A point-of-care testing (CRP&SAA POCT) in reducing the inappropriate use of antibiotics for ARIs in Chinese village clinics.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Germany.
The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.
View Article and Find Full Text PDFJ Phys Chem B
September 2025
Hefei National Research Center for Physical Sciences at the Microscale and Key Laboratory of Precision and Intelligent Chemistry, Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.
Multivalent protein-protein interactions play essential roles in mediating liquid-liquid phase separation (LLPS) that drives biomolecular condensate formation. Here, we systematically investigate how the spatial distribution and relative size of protein binding domains (PBDs) would influence LLPS in a mixture of spherical proteins and RNA single strands by using a patchy-particle polymer model, wherein each protein contains a fixed number of PBDs on the surface distributed closely or sparsely. Intriguingly, we find that LLPS behavior exhibits a nontrivial dependence on the cooperative interplay between PBD distribution and protein size: while sparsely distributed PBDs are more favorable to LLPS for small proteins, closely packed PBDs facilitate LLPS for larger counterparts.
View Article and Find Full Text PDFBrief Bioinform
August 2025
College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, P. R. China.
Drug-induced hepatotoxicity (DIH), characterized by diverse phenotypes and complex mechanisms, remains a critical challenge in drug discovery. To systematically decode this diversity and complexity, we propose a multi-dimensional computational framework integrating molecular structure analysis with disease pathogenesis exploration, focusing on drug-induced intrahepatic cholestasis (DIIC) as a representative DIH subtype. First, a graph-based modularity maximization algorithm identified DIIC risk genes, forming a DIIC module and eight disease pathogenesis clusters.
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