ArticleThe Journal of biological chemistry2009
Hyaluronidase activity of human Hyal1 requires active site acidic and tyrosine residues.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- Mechanism of Hyaluronic Acid Hydrolysis Catalyzed by Snake Venom Hyaluronidase.Journal of chemical information and modeling · 2026Article
- Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators.Science (New York, N.Y.) · 2026Article
- Thiolated Hyaluronic Acid: A Gateway for Targeted Killing of Staphylococcus aureus on the Race for Surface Colonization.Advanced healthcare materials · 2026Article
- Enzyme-Based Anti-Inflammatory Therapeutics for Inflammatory Diseases.Pharmaceutics · 2025Review
- Review
- Proteomic characterization and comparison of the infective and adult life stage secretomes from Necator americanus and Ancylostoma ceylanicum.PLoS neglected tropical diseases · 2025Article
- Production ofJournal of fungi (Basel, Switzerland) · 2024Article
- Isolation, Characterization, Genome Annotation, and Evaluation of Hyaluronidase Inhibitory Activity in Secondary Metabolites ofInternational journal of molecular sciences · 2024Article
- Substitution of acidic residues near the catalytic Glu131 leads to human HYAL1 activity at neutral pH via charge-charge interactions.PloS one · 2024Article
- Lutein derived from Xenostegia tridentata exhibits anticancer activities against A549 lung cancer cells via hyaluronidase inhibition.PloS one · 2024Article
- Influence ofFoods (Basel, Switzerland) · 2023Article
- Endolysosomal impairment by binding of amyloid beta or MAPT/Tau to V-ATPase and rescue via the HYAL-CD44 axis in Alzheimer disease.Autophagy · 2023Article
- Anti-Inflammatory Effect of Izalpinin Derived fromMolecules (Basel, Switzerland) · 2023Article
- Structure of the transmembrane protein 2 (TMEM2) ectodomain and its apparent lack of hyaluronidase activity.Wellcome open research · 2023Article
- Influence of Association on Binding of Disaccharides to YKL-39 and hHyal-1 Enzymes.International journal of molecular sciences · 2022Article
- Enzymatic Hydrolysis of Human Milk Oligosaccharides. The Molecular Mechanism ofACS catalysis · 2022Article
- Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Bioassay-Guided Isolation, Metabolic Profiling, and Docking Studies of Hyaluronidase Inhibitors fromMolecules (Basel, Switzerland) · 2020Article
- Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020Article
- Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hyaluronidases are a family of endolytic glycoside hydrolases that cleave the beta1-4 linkage between N-acetylglucosamine and glucuronic acid in hyaluronan polymers via a substrate-assisted mechanism. In humans, turnover of hyaluronan by this enzyme family is critical for normal extracellular matrix remodeling. However, elevated expression of the Hyal1 isozyme accelerates tumor growth and metastatic progression. In this study, we used structural information, site-directed mutagenesis, and steady state enzyme kinetics to probe molecular determinants of human Hyal1 function. Mutagenesis of active site residues Glu(131) and Tyr(247) to Gln and Phe, respectively, eliminated activity at all hyaluronan concentrations (to 125 microm or 2.5 mg/ml). Conservative mutagenesis of Asp(129) and Tyr(202) significantly impaired catalysis by increases of 5- and 10-fold in apparent K(m) and reductions in V(max) of 95 and 50%, respectively. Tyr(247) and Asp(129) are required for stabilization of the catalytic nucleophile, which arises as a resonance intermediate of N-acetylglucosamine on the substrate. Glu(131) is a likely proton donor for the hydroxyl leaving group. Tyr(202) is a substrate binding determinant. General disulfide reduction had no effect on activity in solution, but enzymatic deglycosylation reduced Hyal1 activity in a time-dependent fashion. Mutagenesis identified Asn(350) glycosylation as the requisite modification. Deletion of the C-terminal epidermal growth factor-like domain, in which Asn(350) is located, also eliminated activity, irrespective of glycosylation. Collectively, these studies define key components of Hyal1 active site catalysis, and structural factors critical for stability. Such detailed understanding will allow rational design of enzyme modulators.
Indexed as
Identifiers
What OpenQuestion holds
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.