In single domain, "standard mechanism" protein inhibitors of serine proteinases, about a dozen residues make contact with the cognate enzyme. The remainder of the molecule, the scaffolding, holds the reactive site region of the inhibitor in a canonical conformation, improves the binding by about six orders of magnitude and protects it from proteolysis. However, the stability and global structure of the scaffolding is irrelevant to inhibition, provided that inhibition is measured much below the melting temperature, Tm.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/0929866054395383 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genome assembly and multiomic analyses reveal insights into flower and bark colors of Lagerstroemia excelsa.
Plant Physiol Biochem
January 2025
Mid-Florida Research and Education Center, Environmental Horticulture Department, University of Florida, 2725 S. Binion Road, Apopka, FL, 32703, USA. Electronic address:
Lagerstroemia excelsa is a unique plant species from China, holds a significant aesthetic and economic value, and plays a crucial role in landscape architecture and horticulture. Thus far, there is little genetic and genomic information available about this species, which limits its use in development of new cultivars. In this study, a high-quality genome map of L.
View Article and Find Full Text PDFMenin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis.
Cell Rep
January 2025
Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen, Fujian, P.R. China; State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, P.R. China. Electronic address:
Menin is a scaffold protein encoded by the Men1 gene, and it interacts with a variety of chromatin regulators to activate or repress cellular processes. The potential importance of menin in immune regulation remains unclear. Here, we report that myeloid deletion of Men1 results in the development of spontaneous pulmonary alveolar proteinosis (PAP).
View Article and Find Full Text PDFA Glutamate Receptor-Like Gene AtGLR25 With Its Unusual Splice Variant Has a Role in Mediating Glutamate-Elicited Changes in Arabidopsis Root Architecture.
Plant Cell Environ
January 2025
College of Resources and Environmental Sciences, Department of Plant Nutrition, China Agricultural University, Beijing, Haidian, China.
The occurrence of external L-glutamate at the Arabidopsis root tip triggers major changes in root architecture, but the mechanism of -L-Glu sensing is unknown. Members of the family of GLUTAMATE RECEPTOR-LIKE (GLR) proteins are known to act as amino acid-gated Ca-permeable channels and to have signalling roles in diverse plant processes. To investigate the possible role of GLRs in the root architectural response to L-Glu, we screened a collection of mutants with T-DNA insertions in each of the 20 AtGLR genes.
View Article and Find Full Text PDFSmall molecule inhibits KCNQ channels with a non-blocking mechanism.
Nat Chem Biol
January 2025
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.
View Article and Find Full Text PDFEpisodic and associative memory from spatial scaffolds in the hippocampus.
Nature
January 2025
Department of Brain and Cognitive Sciences and McGovern Institute, MIT, Cambridge, MA, USA.
Hippocampal circuits in the brain enable two distinct cognitive functions: the construction of spatial maps for navigation, and the storage of sequential episodic memories. Although there have been advances in modelling spatial representations in the hippocampus, we lack good models of its role in episodic memory. Here we present a neocortical-entorhinal-hippocampal network model that implements a high-capacity general associative memory, spatial memory and episodic memory.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!