ArticleThe Journal of biological chemistry2017
Inhibition of Mammalian Glycoprotein YKL-40: IDENTIFICATION OF THE PHYSIOLOGICAL LIGAND.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Chitinase‑3 like‑protein‑1: A potential predictor of cardiovascular disease (Review).Molecular medicine reports · 2024Pooled it
- Article
- Chitinase-3-Like Protein 1 as a Therapeutic Target for Inflammatory Diseases.Biomolecules & therapeutics · 2025Review
- Heparin-binding of the human chitinase-like protein YKL-40 is allosterically modified by chitin oligosaccharides.Biochemistry and biophysics reports · 2025Article
- Darifenacin: a promising chitinase 3-like 1 inhibitor to tackle drug resistance in pancreatic ductal adenocarcinoma.Cancer chemotherapy and pharmacology · 2024Article
- Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers.Cancer cell international · 2024Review
- Investigation of the Circular Transcriptome in Alzheimer's Disease Brain.Journal of molecular neuroscience : MN · 2024Article
- α-Chitosan and β-Oligochitosan Mixtures-Based Formula for In Vitro Assessment of Melanocyte Cells Response.International journal of molecular sciences · 2024Article
- Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer.Experimental & molecular medicine · 2024Review
- Atomic-Resolution Experimental Structural Biology and Molecular Dynamics Simulations of Hyaluronan and Its Complexes.Molecules (Basel, Switzerland) · 2022Review
- Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment.International journal of molecular sciences · 2021Article
- Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- The effects of YKL-40 on angiogenic potential of HUVECs are partly mediated by syndecan-4.International journal of medical sciences · 2021Article
- Chitinases and chitinase-like proteins as biomarkers in neurologic disorders.Neurology(R) neuroimmunology & neuroinflammation · 2021Review
- Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer's disease.Journal of neuroinflammation · 2020Article
- Molecular modeling of the effects of glycosylation on the structure and dynamics of human interferon-gamma.Journal of molecular modeling · 2019Article
- Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection.PLoS pathogens · 2018Article
- Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to-mesenchymal transition through β-catenin/Erk/Akt signaling in gastric cancer.Journal of experimental & clinical cancer research : CR · 2018Article
- An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis.ASN neuroArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well documented association, identification of the lectin's physiological ligand and, accordingly, biological function has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles such as mediating cellular receptors and cell adhesion and migration. Here, we consider the feasibility of polysaccharides, including cello-oligosaccharides, hyaluronan, heparan sulfate, heparin, and chondroitin sulfate, and collagen-like peptides as physiological ligands for YKL-40. We use molecular dynamics simulations to resolve the molecular level recognition mechanisms and calculate the free energy of binding the hypothesized ligands to YKL-40, addressing thermodynamic preference relative to chito-oligosaccharides. Our results suggest that chitohexaose and hyaluronan preferentially bind to YKL-40 over collagen, and hyaluronan is likely the preferred physiological ligand, because the negatively charged hyaluronan shows enhanced affinity for YKL-40 over neutral chitohexaose. Collagen binds in two locations at the YKL-40 surface, potentially related to a role in fibrillar formation. Finally, heparin non-specifically binds at the YKL-40 surface, as predicted from structural studies. Overall, YKL-40 likely binds many natural ligands
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.