dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 50(D1), P. D471 - D479

Published: Oct. 13, 2021

Protein post-translational modifications (PTMs) play an important role in different cellular processes. In view of the importance PTMs functions and massive data accumulated by rapid development mass spectrometry (MS)-based proteomics, this paper presents update dbPTM with over 2 777 000 PTM substrate sites obtained from existing databases manual curation literature, which more than 235 entries are experimentally verified. This has manually curated 42 new modification types that were not included previous version. Due to increasing number studies on mechanism past few years, a great deal upstream regulatory proteins have been revealed. The updated thus collates information merges them into protein-protein interaction network. To enhance understanding association between molecular functions/cellular processes, functional annotations integrated database. addition, PTM-related resources, including annotation prediction tools also renewed. Overall, update, we would like provide users most abundant comprehensive proteins. is now freely accessible at https://awi.cuhk.edu.cn/dbPTM/.

Language: Английский

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Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Language: Английский

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Understanding the extracellular vesicle surface for clinical molecular biology

Journal of Extracellular Vesicles, Journal Year: 2022, Volume and Issue: 11(10)

Published: Oct. 1, 2022

Extracellular vesicles (EVs) are lipid-membrane enclosed nanoparticles that play significant roles in health and disease. EVs abundant body fluids carry an array of molecules (proteins, lipids, nucleic acids glycans) reflect the identity activity their cell-of-origin. While advent high throughput omics technologies has allowed in-depth characterisation EV compositions, how these molecular species spatially distributed within structures is not well appreciated. This particularly true surface where a plethora reported to be both integral peripherally associated membrane. coronal layer or 'atmosphere' surrounds membrane contributes large, highly interactive dynamic area responsible for facilitating interactions with extracellular environment. The harbours parent cells, which likely valuable property context diagnostic liquid biopsies. In this review, we describe current understanding mechanical, electrostatic properties offer biomarker potential contribute interactome.

Language: Английский

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Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(20), P. 15603 - 15671

Published: Sept. 29, 2022

Glycoconjugates are major constituents of mammalian cells that formed via covalent conjugation carbohydrates to other biomolecules like proteins and lipids often expressed on the cell surfaces. Among three classes glycoconjugates, proteoglycans glycoproteins contain glycans linked protein backbone amino acid residues such as Asn for N-linked Ser/Thr O-linked glycans. In glycolipids, a lipid component glycerol, polyisoprenyl pyrophosphate, fatty ester, or sphingolipid. Recently, glycoconjugates have become better structurally defined biosynthetically understood, especially those associated with human diseases, accessible new drug, diagnostic, therapeutic developments. This review describes status advances in biological study applications natural synthetic including proteoglycans, glycoproteins, glycolipids. The scope, limitations, novel methodologies synthesis clinical development vaccines, glyco-remodeled antibodies, glycan-based adjuvants, glycan-specific receptor-mediated drug delivery platforms, etc., their future prospectus discussed.

Language: Английский

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Global functions of O‐glycosylation: promises and challenges in O‐glycobiology

FEBS Journal, Journal Year: 2021, Volume and Issue: 288(24), P. 7183 - 7212

Published: Aug. 4, 2021

Mucin type O‐glycosylation is one of the most diverse types glycosylation, playing essential roles in tissue development and homeostasis. In complex organisms, O‐GalNAc glycans comprise a substantial proportion glycocalyx, with defined functions hemostatic, gastrointestinal, respiratory systems. Furthermore, are important players host–microbe interactions, changes O‐glycan composition associated certain diseases metabolic conditions, which some instances can be used for diagnosis or therapeutic intervention. Breakthroughs O‐glycobiology have gone hand new technologies, such as advancements mass spectrometry, well facilitation genetic engineering mammalian cell lines. High‐throughput O‐glycoproteomics enabled us to draw comprehensive map O‐glycosylation, mining this information has supported definition confirmation related site‐specific O‐glycans. This includes protection from proteolytic cleavage, modulation binding affinity receptor function. Yet, there still much discover, among next challenges will define context‐dependent O‐glycans different stages cellular differentiation, metabolism, host–microbiome disease. review, we present achievements promises glycobiology driven by technological advances analytical methods, engineering, systems biology.

Language: Английский

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Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 27, 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.

Language: Английский

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N-Glycosylation and Inflammation; the Not-So-Sweet Relation

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 27, 2022

Chronic inflammation is the main feature of many long-term inflammatory diseases such as autoimmune diseases, metabolic disorders, and cancer. There a growing number studies in which alterations N-glycosylation have been observed pathophysiological conditions, yet underlying mechanisms that precede N-glycome changes are still sparse. Proinflammatory cytokines shown to alter substrate synthesis pathways well expression glycosyltransferases required for biosynthesis N-glycans. The resulting can further contribute disease pathogenesis through modulation various aspects immune cell processes, including those relevant pathogen recognition fine-tuning response. This review summarizes our current knowledge inflammation-induced changes, with particular focus on specific subsets cells innate adaptive immunity how these affect their effector functions, interactions, signal transduction.

Language: Английский

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Aberrant Sialylation in Cancer: Therapeutic Opportunities

Cancers, Journal Year: 2022, Volume and Issue: 14(17), P. 4248 - 4248

Published: Aug. 31, 2022

The surface of every eukaryotic cell is coated in a thick layer glycans that acts as key interface with the extracellular environment. Cancer cells have different ‘glycan coat’ to healthy and aberrant glycosylation universal feature cancer linked all hallmarks. This means hold huge potential for development new diagnostic therapeutic strategies. One change tumour increased sialylation, both on N-glycans O-glycans, which leads dense forest sialylated structures covering surface. hypersialylation has far-reaching consequences cells, are fundamental growth, metastasis, immune evasion drug resistance. strategies inhibit sialylation represents an important opportunity develop therapeutics. Here, I summarise recent advances target cancer, including sialyltransferase inhibitors Siglecs Selectins, discuss opportunities future.

Language: Английский

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Primary Structure of Glycans by NMR Spectroscopy

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(3), P. 1040 - 1102

Published: Jan. 9, 2023

Glycans, carbohydrate molecules in the realm of biology, are present as biomedically important glycoconjugates and a characteristic aspect is that their structures many instances branched. In determining primary structure glycan, sugar components including absolute configuration ring form, anomeric configuration, linkage(s), sequence, substituents should be elucidated. Solution state NMR spectroscopy offers unique opportunity to resolve all these aspects at atomic resolution. During last two decades, advancement both experiments spectrometer hardware have made it possible unravel more efficiently. These developments applicable glycans include, inter alia, reduce spectral overlap, use selective excitations, record tilted projections multidimensional spectra, acquire spectra by multiple receivers, utilize polarization fast-pulsing techniques, concatenate pulse-sequence modules several single measurement, pure shift correlated devoid scalar couplings, employ stable isotope labeling efficiently obtain homo- and/or heteronuclear correlations, well those rely on dipolar cross-correlated interactions for sequential information. Refined computer programs spin simulation chemical prediction aid structural elucidation glycans, which notorious limited dispersion. Hardware include cryogenically cold probes dynamic nuclear resulting enhanced sensitivity ultrahigh field spectrometers with 1H resonance frequency higher than 1 GHz, thus improving resolution resonances. Taken together, will future make elucidate great detail, thereby forming basis understanding how interact other molecules.

Language: Английский

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Diversification of Glycosyl Compounds via Glycosyl Radicals

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(38)

Published: June 7, 2023

Glycosyl radical functionalization is one of the central topics in synthetic carbohydrate chemistry. Recent advances metal-catalyzed cross-coupling chemistry and metallaphotoredox catalysis provided powerful platforms for glycosyl diversification. In particular, discovery new precursors conjunction with these advanced reaction technologies have significantly expanded space compound synthesis. this Review, we highlight most recent progress area starting from 2021, reports included will be categorized based on different types better clarity.

Language: Английский

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