Article
Chemistry, Physical
Rylee Wander, Andrea M. Kaminski, Zhangjie Wang, Eduardo Stancanelli, Yongmei Xu, Vijayakanth Pagadala, Jine Li, Juno M. Krahn, Truong Quang Pham, Jian Liu, Lars C. Pedersen
Summary: The study presents the crystal structures of 3-OST-5 with substrates and PAP, revealing its substrate specificity and anti-factor Xa activity. The enzyme prefers to sulfate a 6-O-sulfo glucosamine saccharide that is surrounded by glucuronic acid. Additionally, it was found that substrate specificity is not only determined by the side chains of amino acid residues in the active site, but also by the conformational flexibility of 2-O-sulfated iduronic acid in the saccharide substrates.
Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Allergy
Konrad Bork, Karin Wulff, Britta S. Moehl, Lars Steinmueller-Magin, Gunther Witzke, Jochen Hardt, Peter Meinke
Summary: The study identified a novel disease-linked mutation for HAEnCI using whole exome sequencing, which affects HS biosynthesis and likely disrupts cell surface interactions of key players in angioedema formation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Dylan Mah, Yanan Zhu, Guowei Su, Jing Zhao, Ashely Canning, James Gibson, Xuehong Song, Eduardo Stancanelli, Yongmei Xu, Fuming Zhang, Robert J. Linhardt, Jian Liu, Lianchun Wang, Chunyu Wang
Summary: Apolipoprotein E (ApoE)'s epsilon 4 allele is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Heparan sulfate (HS) on the cell surface acts as a cofactor for the interaction between ApoE and LRP1, as well as the prion-like spread of tau pathology between cells. 3-O-sulfated HS has been linked to AD through its interaction with tau, and increased levels of 3-O-sulfated HS and 3-O-sulfotransferases have been observed in the AD brain. This study characterizes the interactions between ApoE and HS in different ApoE isoforms, and suggests that the interplay between 3-O-sulfated HS, tau, and ApoE isoforms may modulate AD risk.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Elena Carava, Paola Moretto, Ilaria Caon, Arianna Parnigoni, Alberto Passi, Evgenia Karousou, Davide Vigetti, Jessica Canino, Ilaria Canobbio, Manuela Viola
Summary: Cardiovascular diseases result from various risk factors, and inflammation induced by cytokines like TNF-alpha may lead to changes in vessel matrix composition without affecting cell proliferation or migration.
Article
Clinical Neurology
Natalia Perez-Lopez, Carla Martin, Beatriz Garcia, Maria Pilar Solis-Hernandez, David Rodriguez, Ignacio Alcalde, Jesus Merayo, Ivan Fernandez-Vega, Luis M. Quiros
Summary: The saccharide chains of heparan sulfate play a crucial role in the pathogenesis of Alzheimer's disease, with differential transcription of biosynthetic genes observed in different brain regions and stages of AD pathology. The study revealed more alterations in gene transcription in moderate AD patients compared to mild cases, with fewer changes in genes related to early stages of synthesis in severe patients and an overexpression of late-stage genes. These alterations correlated with progressive brain atrophy, particularly in the cerebellum, and were consistent with immunohistochemical detection of certain heparan sulfate epitopes.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lingbo Sun, Andriana Konstantinidi, Zilu Ye, Rebecca Nason, Yuecheng Zhang, Christian Bull, Barbro Kahl-Knutson, Lars Hansen, Hakon Leffler, Sergey Y. Vakhrushev, Zhang Yang, Henrik Clausen, Yoshiki Narimatsu
Summary: Researchers engineered sulfotransferase genes in HEK293 cells to achieve sulfation modification of O-glycans. They used this engineered cell library to study the binding specificity between galectin-4 and sulfated O-glycans.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hao Cui, Zhaoguang Wang, Tianji Zhang, Jin-ping Li, Jianping Fang
Summary: The translation explores the role of Heparan sulfate (HS) in protein recognition and interaction, highlighting the importance of specific sulfation and epimerization patterns modulated by Golgi-localized enzymes. The study investigates the effects of restoring Hsepi in mutant MEF cells, showing increased IdoA residues and rescued cell signaling, although Hsepi knockout did not influence cellular transport or enzymatic activity of 2OST. These findings suggest potential differences in regulatory mechanisms for 2OST and Hsepi.
Article
Chemistry, Physical
Haiyi Chen, Yu Kang, Mojie Duan, Tingjun Hou
Summary: The study revealed that the presence of heparan sulfate is crucial for the binding between the spike protein of SARS-CoV-2 and host ACE2, while the stability of the T470-F490 loop and hydrophobic interactions play key roles in the binding process.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Applied
Tianji Zhang, Mingjia Yu, Honglian Li, Marco Maccarana, Wei Zhang, Deling Shi, Ying Kan, Xiao Zhang, Lianli Chi, Ulf Lindahl, Hongmei Li, Jin-ping Li, Tianwei Tan
Summary: This study investigated the functional interactions between glucuronyl 5-epimerase (Hsepi) and hexuronyl 2-O-sulfotransferase (Hs2st) and glucosaminyl 6-O-sulfotransferase (Hs6st) using an isotope exchange approach. The results showed that the binding of these enzymes plays an important role in the efficiency of substrate conversion. Furthermore, experimental evidence suggested the formation of a functional complex between Hsepi and Hs6st in cells, and the inability to achieve simultaneous 2-O and 6-O sulfation in vitro.
CARBOHYDRATE POLYMERS
(2023)
Article
Immunology
Maria del Pilar Huby Vidaurre, Baron K. Osborn, Kaylie D. Lowak, Michelle M. McDonald, Yao-Wei W. Wang, Veda Pa, Jillian R. Richter, Yongmei Xu, Katelyn Arnold, Jian Liu, Jessica C. Cardenas
Summary: A synthetic 3-O-sulfated heparan sulfate 12-mer, dekaparin, has been found to have anti-thrombotic and anti-inflammatory properties, which can alleviate organ injury following major trauma and hemorrhagic shock.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
L. Baert, B. Manfroi, M. Quintero, O. Chavarria, P. V. Barbon, E. Clement, A. Zeller, T. Van Kuppevelt, N. Sturm, J. Moreaux, A. Tveita, B. Bogen, T. McKee, B. Huard
Summary: Multiple myeloma is a hematological neoplasm derived from plasma cells in the bone marrow. A subpopulation of cells called 10e4(+) cells, which have high resistance to multiple myeloma drugs, bind to the protein APRIL through heparan sulfate chains on syndecan-1. These cells have high proliferation activity and are able to form colonies in 3D cultures. They can develop in the bone marrow after intravenous injection and become more resistant to drugs after treatment. The enzyme HS3ST3a1 plays a role in modifying syndecan-1 to confer reactivity to 10e4 and APRIL binding. Targeting this enzyme could potentially improve drug resistance control in multiple myeloma.
Article
Biology
Miaomiao Li, Chih Yean Ong, Christophe J. Langouet-Astrie, Lisi Tan, Ashwni Verma, Yimu Yang, Xiaoxiao Zhang, Dhaval K. Shah, Eric P. Schmidt, Ding Xu
Summary: This study reveals the important role of heparan sulfate (HS) in RAGE oligomerization and its necessity for RAGE signaling. Blocking HS-RAGE interaction can inhibit RAGE signaling. Furthermore, inhibiting HS-RAGE interaction genetically and pharmacologically provides an alternative strategy to antagonize RAGE. Additionally, Ager(AHA/AHA) mice may serve as a cleaner genetic model to study the physiological roles of RAGE in vivo compared to Ager(-/-) mice.
Review
Cell Biology
Amrita Basu, Neil G. Patel, Elijah D. Nicholson, Ryan J. Weiss
Summary: Glycosaminoglycans (GAGs) are long polysaccharides found on the cell surface and extracellular matrix of animal cells, and play important roles in cellular processes and diseases. GAGs are complex molecules with extensive structural and functional heterogeneity, and their biosynthesis is a non-template driven process involving a group of enzymes. Due to their key roles in cell homeostasis and disease, targeting the assembly and function of GAGs is of great interest as a therapeutic approach.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Balaji Nagarajan, Umesh R. Desai
Summary: This study discovered novel compact topologies of heparan sulfate (HS) that are influenced by the 3-O-sulfation of cis-idoA residues. The transition in HS topology is driven by rotations that reduce like-charge repulsion, release water molecules, and establish specific interactions. These findings reveal a dynamic sulfation code in natural HS that could be utilized for selective recognition of target proteins.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Virology
Yan Xu, Pierre Martinez, Karin Seron, Guangxiang Luo, Fabrice Allain, Jean Dubuisson, Sandrine Belouzard
JOURNAL OF VIROLOGY
(2015)
Article
Immunology
Piotr Szpakowski, Franck Biet, Camille Locht, MaBgorzata Paszkiewicz, Wieslawa Rudnicka, Magdalena Druszczynska, Fabrice Allain, Marek Fol, Joel Pestel, Magdalena Kowalewicz-Kulbat
JOURNAL OF IMMUNOLOGY RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Anne-Sophie Sikora, Charles Hellec, Mathieu Carpentier, Pierre Martinez, Maxime Delos, Agnes Denys, Fabrice Allain
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Maxime Delos, Charles Hellec, Francois Foulquier, Mathieu Carpentier, Fabrice Allain, Agnes Denys
Article
Biochemistry & Molecular Biology
Maxime Delos, Francois Foulquier, Charles Hellec, Dorothee Vicogne, Alexandre Fifre, Mathieu Carpentier, Dulce Papy-Garcia, Fabrice Allain, Agnes Denys
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2018)
Article
Multidisciplinary Sciences
Charles Hellec, Maxime Delos, Mathieu Carpentier, Agnes Denys, Fabrice Allain
Article
Biochemistry & Molecular Biology
Pierre Martinez, Agnes Denys, Maxime Delos, Anne-Sophie Sikora, Mathieu Carpentier, Sylvain Julien, Joel Pestel, Fabrice Allain
Article
Biochemistry & Molecular Biology
Mathieu Carpentier, Agnes Denys, Fabrice Allain, Gerard Vergoten
GLYCOCONJUGATE JOURNAL
(2014)
Article
Multidisciplinary Sciences
Cyprien Jaillet, Willy Morelle, Marie-Christine Slomianny, Vincent Paget, Georges Tarlet, Valerie Buard, Sonia Selbonne, Fanny Caffin, Emilie Rannou, Pierre Martinez, Agnes Francois, Francois Foulquier, Fabrice Allain, Fabien Milliat, Olivier Guipaud
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Charles Hellec, Mariama Diawara, Mathieu Carpentier, Agnes Denys, Fabrice Allain
Article
Biochemistry & Molecular Biology
Julien Cherfils-Vicini, Charlene Iltis, Ludovic Cervera, Sabrina Pisano, Olivier Croce, Nori Sadouni, Balazs Gyorffy, Romy Collet, Valerie M. Renault, Martin Rey-Millet, Carlo Leonetti, Pasquale Zizza, Fabrice Allain, Francois Ghiringhelli, Nicolas Soubeiran, Marina Shkreli, Eric Vivier, Annamaria Biroccio, Eric Gilson
Review
Oncology
Agnes Denys, Fabrice Allain
FRONTIERS IN ONCOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Yoshiko Takeda-Uchimura, Midori Ikezaki, Tomoya O. Akama, Kaho Nishioka, Yoshito Ihara, Fabrice Allain, Kazuchika Nishitsuji, Kenji Uchimura
Summary: In this study, it was found that CL40-positive sialylated and sulfated glycans are abundant in the pleural mesothelium and are synthesized complementarily by GlcNAc6ST2 and GlcNAc6ST3 under physiological conditions.
Article
Toxicology
Hela Hacine-Gherbi, Agnes Denys, Mathieu Carpentier, Arnaud Heysen, Pierrick Duflot, Pierre Lanos, Fabrice Allain
TOXICOLOGY REPORTS
(2017)