Biomolecular Condensation of Trypsin Prevents Autolysis and Promotes Ca2+‐Mediated Activation of Esterase Activity DOI Creative Commons

Chinmaya Kumar Patel,

Tushar Kanti Mukherjee

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 2, 2024

Abstract The presence of Ca 2+ ions is known to facilitates the biocatalytic activity trypsin-like serine proteases via structural stabilization against thermal denaturation and autolysis. Herein, we report a new hidden regulatory role in catalytic pathways trypsin α-chymotrypsin under physiological conditions. We discovered that macromolecular crowding promotes spontaneous homotypic condensation native liquid-liquid phase separation yield membraneless condensates/droplets broad range concentrations, pH, temperature. These condensates are stabilized by multivalent hydrophobic interactions between short patches residues. Importantly, no liquid-to-solid-like transition has been observed over period 14 days, indicating intrigrity phase-separated within droplets. Structural insights revealed minimal conformational perturbation upon separation. Interestingly, found binding calcium loop reversibly regulates biomolecular α-chymotrypsin. While -bound ineffective undergo LLPS form condensate, its removal similar experimental More importantly, show effectively prevents autolysis at conditions preserve native-like esterase whereas free loses 86% initial activity. In addition, it responds -dependent activation even after days storage while failed do so. Our findings indicate act as media prevent premature activation, same time their active conformations. present study highlights an important aspect which cells can spatio-temporally regulate efficacy -signalling.

Язык: Английский

Peroxidase-Mimicking DNAzymes as Receptors for Label-Free Discriminating Heavy Metal Ions by Chemiluminescence Sensor Arrays DOI

Mengmeng Wu,

Bing Yang, Lu Shi

и другие.

Analytical Chemistry, Год журнала: 2023, Номер 95(6), С. 3486 - 3492

Опубликована: Фев. 3, 2023

Receptors are crucial to the analytical performance of sensor arrays. Different from previous receptors in arrays, herein, peroxidase-mimicking DNAzymes were innovatively used as develop a label-free chemiluminescence array for discriminating various heavy metal ions complex samples. The composed functional oligonucleotides and hemin, including G-triplex-hemin DNAzyme (G3-DNAzyme), G-quadruplex-hemin (G4-DNAzyme), dimer (dG4-DNAzyme). Circular dichroism (CD) spectroscopy demonstrated that different diversely affect conformation G-quadruplex G-triplex, resulting change activity DNAzyme. Thus, unique fingerprints formed easily discriminate seven kinds by principal component analysis (PCA) within 20 min. discrimination unknown tap water further confirmed its ability multiple ions. Moreover, it will not bring pollution due good biocompatibility DNA. Therefore, only merely offers label-free, rapid, environment-friendly, cheap (1.49 $) assay but also comes up with an innovative way developing

Язык: Английский

Процитировано

27
Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide DOI Creative Commons
Stuart A. Harrison,

William L. Webb,

Hanadi Rammu

и другие.

Life, Год журнала: 2023, Номер 13(5), С. 1177 - 1177

Опубликована: Май 12, 2023

A protometabolic approach to the origins of life assumes that conserved biochemistry metabolism has direct continuity with prebiotic chemistry. One most important amino acids in modern biology is aspartic acid, serving as a nodal metabolite for synthesis many other essential biomolecules. Aspartate’s complicated by instability its precursor, oxaloacetate. In this paper, we show use biologically relevant cofactor pyridoxamine, supported metal ion catalysis, sufficiently fast offset oxaloacetate’s degradation. Cu2+-catalysed transamination oxaloacetate pyridoxamine achieves around 5% yield within 1 h, and can operate across broad range pH, temperature, pressure. addition, downstream product β-alanine may also take place same reaction system at very low yields, directly mimicking an archaeal route. Amino group transfer pyridoxal shown from aspartate alanine, but reverse (alanine aspartate) shows poor yield. Overall, our results related indeed be synthesised via pathways foreshadow presence simple ions.

Язык: Английский

Процитировано

17
Calcium carbonate-actuated ion homeostasis perturbator for oxidative damage-augmented Ca2+/Mg2+ interference therapy DOI
Jiansen Huang, Jie He, Jie Wang

и другие.

Biomaterials, Год журнала: 2023, Номер 302, С. 122340 - 122340

Опубликована: Сен. 25, 2023

Язык: Английский

Процитировано

15
Membrane transporters in cell physiology, cancer metabolism and drug response DOI Creative Commons
Sara Alam,

Emily Doherty,

Paula Ortega-Prieto

и другие.

Disease Models & Mechanisms, Год журнала: 2023, Номер 16(11)

Опубликована: Ноя. 1, 2023

ABSTRACT By controlling the passage of small molecules across lipid bilayers, membrane transporters influence not only uptake and efflux nutrients, but also metabolic state cell. With more than 450 members, Solute Carriers (SLCs) are largest transporter super-family, clustering into families with different substrate specificities regulatory properties. Cells types are, therefore, able to tailor their expression signatures depending on requirements, physiological importance these proteins is illustrated by mis-regulation in a number disease states. In cancer, heterogeneous, SLC family has been shown facilitate accumulation biomass, redox homeostasis, mediate crosstalk other cell within tumour microenvironment. This Review explores roles malignant settings, how can affect drug response, through either indirect modulation sensitivity or direct transport small-molecule therapeutic compounds cells.

Язык: Английский

Процитировано

15
A PD‐L1‐targeting Regulator for Metabolic Reprogramming to Enhance Glutamine Inhibition‐Mediated Synergistic Antitumor Metabolic and Immune Therapy DOI Open Access
Xiao‐Kang Jin,

Shi‐Man Zhang,

Jun‐Long Liang

и другие.

Advanced Materials, Год журнала: 2023, Номер 36(6)

Опубликована: Ноя. 28, 2023

Abstract Inhibition of glutamine metabolism in tumor cells can cause metabolic compensation‐mediated glycolysis enhancement and PD‐L1 upregulation‐induced immune evasion, significantly limiting the therapeutic efficacy inhibitors. Here, inspired by specific binding receptor ligand, a PD‐L1‐targeting regulator (PMIR) are constructed decorating glutaminase inhibitor (BPTES)‐loading zeolitic imidazolate framework (ZIF) with peptides for regulating within microenvironment (TME) to improve immunotherapy. At sites, PMIR inhibits elevating levels TME function cells. Ingeniously, accompanying upregulation on causes self‐amplifying accumulation through targeting, while also blocking PD‐L1, which has effects converting enemies into friends. Meanwhile, exactly offsets compensatory glycolysis, disrupting redox homeostasis via cooperation components ZIF BPTES. These together immunogenic cell death relieve PD‐L1‐mediated further reshaping immunosuppressive evoking robust responses effectively suppress bilateral progression metastasis. This work proposes rational strategy surmount obstacles inhibition boosting existing clinical treatments.

Язык: Английский

Процитировано

14
Flexible MXene-conjugated polymer nanoarchitectures: Current developments and future frontiers in battery technology DOI
Sowjanya Vallem, Sada Venkateswarlu, Seunghyun Song

и другие.

Coordination Chemistry Reviews, Год журнала: 2024, Номер 510, С. 215778 - 215778

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

5
The ability of pentose pathways to form all essential metabolites provides clues to the origins of metabolism DOI Creative Commons
Steffen N. Lindner, Markus Ralser

PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002996 - e3002996

Опубликована: Янв. 10, 2025

The structure of the early metabolic network is unknown. Here, we report that when considered together, pentose utilization pathways form all life-essential precursors. We speculate chemistry preserved in metabolism could therefore have been a central structural element metabolism.

Язык: Английский

Процитировано

0
Predicting substrates for orphan solute carrier proteins using multi-omics datasets DOI Creative Commons
Yimo Zhang, Simon Newstead, Peter Sarkies

и другие.

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 11, 2025

Abstract Solute carriers (SLC) are integral membrane proteins responsible for transporting a wide variety of metabolites, signaling molecules and drugs across cellular membranes. Despite key roles in metabolism, pharmacology, around one third SLC ‘orphans’ whose substrates unknown. Experimental determination is technically challenging, given the range possible physiological candidates. Here, we develop predictive algorithm to identify correlations between expression levels intracellular metabolite concentrations by leveraging existing cancer multi-omics datasets. Our predictions recovered known SLC-substrate pairs with high sensitivity specificity compared simulated random pairs. CRISPR-Cas9 dependency screen data metabolic pathway adjacency further improved performance our algorithm. In parallel, combined drug profiles predict new SLC-drug interactions. Together, provide novel bioinformatic pipeline substrate SLCs, offering opportunities de-orphanise SLCs important implications understanding their health disease.

Язык: Английский

Процитировано

0
Fabrication of imine-based COFs with different linker lengths for HRP and GOx immobilization and colorimetric detection of glucose and H2O2 DOI
Ziqi Meng, Zhichao Yang,

Chunhuan Xu

и другие.

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Год журнала: 2025, Номер 333, С. 125892 - 125892

Опубликована: Фев. 12, 2025

Язык: Английский

Процитировано

0
Identification of biomarkers in Alzheimer’s disease and COVID-19 by bioinformatics combining single-cell data analysis and machine learning algorithms DOI Creative Commons
Juntu Li,

Linfeng Tao,

Yanyou Zhou

и другие.

PLoS ONE, Год журнала: 2025, Номер 20(2), С. e0317915 - e0317915

Опубликована: Фев. 18, 2025

Background Since its emergence in 2019, COVID-19 has become a global epidemic. Several studies have suggested link between Alzheimer’s disease (AD) and COVID-19. However, there is little research into the mechanisms underlying these phenomena. Therefore, we conducted this study to identify key genes associated with AD, evaluate their correlation immune cells characteristics metabolic pathways. Methods Transcriptome analyses were used common biomolecular markers of AD Differential expression analysis weighted gene co-expression network (WGCNA) performed on chip datasets (GSE213313, GSE5281, GSE63060) from patients both conditions. Gene ontology (GO) enrichment identified molecular mechanisms. The core using machine learning. Subsequently, evaluated relationship Finally, our findings validated through single-cell analysis. Results 484 differentially expressed (DEGs) by taking intersection black module, containing 132 genes, showed highest association two diseases according WGCNA. GO revealed that mainly affect inflammation, cytokines, immune-related functions, signaling pathways related metal ions. Additionally, learning approach eight genes. We links also found EIF3H oxidative phosphorylation. Conclusion This identifies shared pathways, alterations, changes potentially contributing pathogenesis AD.

Язык: Английский

Процитировано

0