Glycobiology最新文献

Structural characterization and insights into the formation of N-acetylglucosaminylasparagine and its derivatives in NGLY1-deficient models and patients. ngly1缺陷模型和患者中n -乙酰氨基葡萄糖天冬氨酸及其衍生物的结构表征和形成的见解。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-10-13 DOI: 10.1093/glycob/cwaf065

Hiroto Hirayama, Yuriko Tachida, Reiko Fujinawa, Makoto Asahina, Megumi Hirayama, Tomohiro Andou, Masaya Usui, Tadashi Suzuki

{"title":"Structural characterization and insights into the formation of N-acetylglucosaminylasparagine and its derivatives in NGLY1-deficient models and patients.","authors":"Hiroto Hirayama, Yuriko Tachida, Reiko Fujinawa, Makoto Asahina, Megumi Hirayama, Tomohiro Andou, Masaya Usui, Tadashi Suzuki","doi":"10.1093/glycob/cwaf065","DOIUrl":"https://doi.org/10.1093/glycob/cwaf065","url":null,"abstract":"Cytosolic peptide:N-glycanase (PNGase/NGLY1 in mammals), a widely conserved amidase in eukaryotes, catalyzes the removal of N-glycans from glycoproteins and contributes to the quality control system for nascent glycoproteins. Since the first report of a patient with an autosomal recessive genetic disorder caused by NGLY1 deficiency in 2012, over 150 cases have been identified globally. Among the potential biomarkers for NGLY1 deficiency, Asn-linked mono/oligosaccharides-Asn-GlcNAc and Asn-HexNAc-Hex-NeuAc-have emerged as the most consistently and markedly elevated molecules in the plasma or urine of affected patients. This study examined the Asn-GlcNAc biosynthetic pathway, demonstrating that cytosolic endo-β-N-acetylglucosaminidase (ENGase), the proteasome, and peptidases are essential for its generation. NGLY1-deficient models and patients exhibited accumulation of novel elongated forms of Asn-GlcNAc, including Asn-GlcNAc-GalNAc, Asn-GlcNAc-Gal, and Asn-GlcNAc-Gal-NeuAc, in cells, culture supernatant, plasma, and urine. Our findings indicate that Asn-GlcNAc and Asn-oligosaccharides (Asn-OSs) may serve as promising diagnostic tools for NGLY1 deficiency.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Origins and evolution of the essentials of glycobiology textbook. 糖生物学教材的起源与演变。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-10-11 DOI: 10.1093/glycob/cwaf062

Ajit Varki

引用次数: 0

The Importance of N- and O-Glycosylation of Brain Cell Surface Glycoproteins. 脑细胞表面糖蛋白N和o糖基化的重要性。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-10-10 DOI: 10.1093/glycob/cwaf054

Maxence Noel, Yumi M Zürcher, Ea K C Tulin, Richard D Cummings

引用次数: 0

Platform for identifying Human Glycan-Specific Antibodies Against Bacterial Pathogens using Synthetic Glycan Fragments. 利用合成聚糖片段鉴定抗细菌病原体的人聚糖特异性抗体的平台。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-10-10 DOI: 10.1093/glycob/cwaf064

A Robin Temming, Mathieu Claireaux, Gius Kerster, Silvie E Groenewege, Thijs Voskuilen, Zhen Wang, Jeroen D C Codée, Marit J Gils, Nina M Sorge

{"title":"Platform for identifying Human Glycan-Specific Antibodies Against Bacterial Pathogens using Synthetic Glycan Fragments.","authors":"A Robin Temming, Mathieu Claireaux, Gius Kerster, Silvie E Groenewege, Thijs Voskuilen, Zhen Wang, Jeroen D C Codée, Marit J Gils, Nina M Sorge","doi":"10.1093/glycob/cwaf064","DOIUrl":"https://doi.org/10.1093/glycob/cwaf064","url":null,"abstract":"Bacterial infections represent a substantial global health challenge, impacting both human and veterinary health. The ongoing evolution of antibiotic-resistant pathogens, coupled with limited new antibiotic discoveries, urges the need for alternative strategies to treat and prevent these infections. Passive immunization with monoclonal antibodies (mAbs) is gaining interest as a promising alternative. Here, we report an experimental pipeline for generating human mAbs from healthy donor B cells using synthetic mimics of complex bacterial glycans. We identified functional mAbs recognizing discrete and unique epitopes on the surface glycans of two bacterial priority pathogens; Staphylococcus aureus and Streptococcus pyogenes. The use of chemically-defined synthetic glycans was critical for the discovery and systematic characterization of mAbs. From a heterogeneous mix of B cell specificities, antibody sequences were identified, leading to the production of mAbs with distinct reactivities against immunodominant but also to less common or even masked epitopes. The pipeline can be adapted to different glycan targets, donor material or specific antibody isotypes. This work thereby paves the way for the discovery of glycan-specific mAbs with clinical relevance to treat, prevent or diagnose infections with S. aureus, S. pyogenes or other bacterial pathogens.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tandem domains differentially affect enzyme activity in the sialidases of Glaesserella parasuis, Clostridium perfringens, and Bifidobacterium bifidum. 串联结构域对副猪绿脓杆菌、产气荚膜梭菌和两歧双歧杆菌唾液酸酶活性的影响是不同的。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-10-08 DOI: 10.1093/glycob/cwaf049

Madhu Lata, Shilpee Pal, Srikrishna Subramanian, T N C Ramya

{"title":"Tandem domains differentially affect enzyme activity in the sialidases of Glaesserella parasuis, Clostridium perfringens, and Bifidobacterium bifidum.","authors":"Madhu Lata, Shilpee Pal, Srikrishna Subramanian, T N C Ramya","doi":"10.1093/glycob/cwaf049","DOIUrl":"https://doi.org/10.1093/glycob/cwaf049","url":null,"abstract":"Carbohydrate-active enzymes are often associated in tandem with various functional and structural domains, including hydrolytic enzymes, carbohydrate-binding modules, lectin domains, domains of unknown function, signal peptides, and immunoglobulin folds. Among these, carbohydrate-binding modules and lectin domains are well known to influence carbohydrate-active enzyme activity. Here, we investigated the impact of naturally occurring tandem domains on the hydrolytic activity of two well-characterized multi-domain sialidases: Bifidobacterium bifidum sialidase (BbSia2) and Glaesserella parasuis sialidase (HpNanH). We found that the sialidase activity of the BbSia2 catalytic domain remained unaffected upon deletion of its naturally occurring tandem domains. In contrast, deleting the naturally occurring tandem domains of HpNanH significantly reduced its sialidase activity. We also found that the non-native tandem placement of a previously reported sialic acid-binding module, MU3, enhanced the sialidase activity of the HpNanH catalytic domain, with the C-terminal positioning of MU3 providing a greater enhancement. However, the non-native tandem placement of MU3 or the non-catalytic tandem domains of HpNanH failed to enhance the sialidase activity of the catalytic domain of another well-characterized sialidase - Clostridium perfringens sialidase (CpNanI). These results highlight the complex and context-dependent roles of tandem domains in modulating carbohydrate-active enzyme activity and have implications for enzyme engineering studies.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Production and inhibition of human Heparan 6-O-Endosulfatase SULF1. 人肝素6- o -内酯酶SULF1的产生和抑制。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-09-30 DOI: 10.1093/glycob/cwaf059

Reem Aljuhani, Julius Benicky, Aswini Panigrahi, Pritha Mukherjee, Miloslav Sanda, Shiya Zhu, Zora Nováková, Vitor H Pomin, Jian Liu, Bruce Davidson, Cyril Bařinka, Radoslav Goldman

{"title":"Production and inhibition of human Heparan 6-O-Endosulfatase SULF1.","authors":"Reem Aljuhani, Julius Benicky, Aswini Panigrahi, Pritha Mukherjee, Miloslav Sanda, Shiya Zhu, Zora Nováková, Vitor H Pomin, Jian Liu, Bruce Davidson, Cyril Bařinka, Radoslav Goldman","doi":"10.1093/glycob/cwaf059","DOIUrl":"https://doi.org/10.1093/glycob/cwaf059","url":null,"abstract":"SULF1, a human extracellular heparan 6-O-endosulfatase isoform 1, plays a critical role in embryonic development and cancer progression by modulating the 6-O-sulfation of heparan sulfate proteoglycans. However, limited recombinant protein production has hindered structural and functional characterization. To address this issue, we optimized SULF1 expression in HEK293F and HEK293T cells. We achieved yields of 2.2 mg/L of culture media after Ni2+-affinity purification of greater than 80% purity, representing a substantial improvement compared to the reported expression systems. We demonstrated that co-expression of sulfatase-modifying factor 1 in this expression system is essential for enhancing SULF1 enzymatic activity, which depends on conversion of active site cysteine to Cα-formylglycine and the presence of a Ca2+ ion. We further showed that a marine fucosylated chondroitin sulfate polymer isolated from the sea cucumber Holothuria floridana inhibits SULF1 enzymatic activity with IC50 of 0.05 ± 0.006 μg/mL and 0.07 ± 0.008 μg/mL for the GlcNS6S-GlcA-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S-GlcA and 4-methylumbelliferyl sulfate substrates, respectively. Kinetic analysis revealed a mixed-mode inhibition, characterized by alterations in Vmax at all inhibitor concentrations and Km at high inhibitor concentrations. Efficient SULF1 production also enabled us to develop specific monoclonal antibodies, which confirmed SULF1 expression in the stroma of head and neck squamous cell cancer tissues. Collectively, this study provides an efficient workflow for the production of active human SULF1, investigates SULF1 inhibitors, and characterizes anti-SULF1 monoclonal antibodies, which will support further studies of this enzyme in various pathophysiological conditions.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Hydrophilic Domain of HSulf Endosulfatases: An Intrinsically Disordered Region Governing Enzyme Functions and Therapeutic Potential. 硫内酯酶的亲水结构域：控制酶功能和治疗潜力的内在无序区域。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-09-26 DOI: 10.1093/glycob/cwaf060

C Demongin, J Tao, N El Omrani, K Uchimura, N Basdevant, R Daniel

{"title":"The Hydrophilic Domain of HSulf Endosulfatases: An Intrinsically Disordered Region Governing Enzyme Functions and Therapeutic Potential.","authors":"C Demongin, J Tao, N El Omrani, K Uchimura, N Basdevant, R Daniel","doi":"10.1093/glycob/cwaf060","DOIUrl":"https://doi.org/10.1093/glycob/cwaf060","url":null,"abstract":"Human extracellular endosulfatases HSulf-1 and HSulf-2 catalyze the selective 6-O-desulfation of heparan sulfate (HS), critically shaping the sulfation code that governs glycosaminoglycan (GAG)-mediated signaling. A unique feature of these enzymes is their hydrophilic domain (HD), an intrinsically disordered, non-conserved segment absent from all other human sulfatases. Despite lacking homology to known protein domains, the HD has emerged as a key regulatory module for substrate recognition, enzyme localization, and processive activity along HS chains. In this review, we dissect the structural and functional roles of the HD, with emphasis on its dynamic interaction with HS motifs and potential modulation of protein-GAG complexes. We also explore how its intrinsically disordered nature may confer conformational flexibility advantageous for navigating the complex landscape of extracellular glycans. Given the implication of HSulfs in diverse physiological and pathological contexts, including cancer, the HD presents a promising therapeutic target for the selective inhibition of endosulfatase activity. We discuss the challenges and perspectives in targeting intrinsically disordered regions (IDRs) in GAG-binding proteins, and highlight how the HD of HSulfs provides a paradigmatic example of non-canonical domains orchestrating fine-tuned GAG editing in the extracellular matrix.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a concise and rapid cell-based functional assay for evaluating human Dectin-1 antagonists. 建立一种简明快速的基于细胞的功能检测方法来评估人Dectin-1拮抗剂。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-09-03 DOI: 10.1093/glycob/cwaf050

Rui Tada, Naoki Arima, Kazuki Chiba, Taiki Koenuma, Takashi Kanno, Shigeru Kakuta, Yoichiro Iwakura, Yoshiyuki Adachi

{"title":"Development of a concise and rapid cell-based functional assay for evaluating human Dectin-1 antagonists.","authors":"Rui Tada, Naoki Arima, Kazuki Chiba, Taiki Koenuma, Takashi Kanno, Shigeru Kakuta, Yoichiro Iwakura, Yoshiyuki Adachi","doi":"10.1093/glycob/cwaf050","DOIUrl":"10.1093/glycob/cwaf050","url":null,"abstract":"Dectin-1, a C-type lectin receptor that recognizes β-glucans, plays a vital role in antifungal immunity and is involved in inflammatory diseases and cancer, making it a promising therapeutic target for antagonists. However, current evaluations of these antagonists often depend on binding inhibition assays, which may not accurately reflect physiological functional suppression. This study addresses the need for a rapid, functional, cell-based assay for human Dectin-1 (hDectin-1) antagonists. We describe the development and validation of such an assay using THP-1 cells stably expressing hDectin-1 (dTHP-1 cells), which produce TNF-α upon Dectin-1 activation by depleted Zymosan (dZymosan). We established optimal assay conditions as 10 μg/mL dZymosan stimulation for 4 h. Under these conditions, laminarin, a soluble β-glucan, inhibited dZymosan-induced TNF-α production in a dose-dependent manner. This inhibition was specific, as Dextran T40, a non-Dectin-1-binding polysaccharide, had no inhibitory effect on dZymosan-induced responses. This novel, concise (4-hour) assay system directly measures the key physiological outcomes of Dectin-1 signaling, offering a significant improvement over binding-based assays. This provides a valuable platform for screening and characterizing hDectin-1 antagonists, facilitating the development of new therapeutics for Dectin-1-related pathologies.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remembering Stuart Kornfeld. 记住斯图尔特·科恩菲尔德。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-09-03 DOI: 10.1093/glycob/cwaf055

引用次数: 0

Regulatory mechanisms of core fucosylation and its progress in cancer therapy: from inhibitor development to antibody engineering. 核心聚焦的调控机制及其在癌症治疗中的进展：从抑制剂开发到抗体工程。

IF 3.3 3区生物学

Glycobiology Pub Date : 2025-09-03 DOI: 10.1093/glycob/cwaf053

Yujia Xue, Yiping Tao, Qian Lin, Xiyan Tong, Hongnv Yu

{"title":"Regulatory mechanisms of core fucosylation and its progress in cancer therapy: from inhibitor development to antibody engineering.","authors":"Yujia Xue, Yiping Tao, Qian Lin, Xiyan Tong, Hongnv Yu","doi":"10.1093/glycob/cwaf053","DOIUrl":"10.1093/glycob/cwaf053","url":null,"abstract":"Core fucosyltransferase is crucial for core fucosylation modification, and its expression is upregulated in various types of cancers. This upregualtion is involved in tumorigenesis and development as well as closely related to cancer diagnosis and prognosis. In recent years, core fucosylation pathway has been extensively studied, which is imperative for the development of antibodies targeting core fucosylation. This study focuses on the regulatory mechanism of core fucosylation and summarizes the research results of related inhibitors, including methods to inhibit substrate and develop fucosyltransferase 8 inhibitors. This study also comprehensively reviews preparation techniques for deglycosylated antibodies, including gene-editing technology, exogenous addition of soluble RNA, bicistronic gene design, and synthesis of glycosylation inhibitors. Moreover, the current challenges in this field are also investigated in this study, and future research directions are proposed to provide a comprehensive reference for the research on core fucosylation in cancer therapy and related antibody engineering fields.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0