ArticleThe Journal of biological chemistry2010
Catalytic mechanism of heparinase II investigated by site-directed mutagenesis and the crystal structure with its substrate.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium.Life science alliance · 2026Article
- Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 2.4-Å structure of the double-ringScience advances · 2022Article
- Discovery of exolytic heparinases and their catalytic mechanism and potential application.Nature communications · 2021Article
- Chemical O-sulfation of N-sulfoheparosan: a route to rare N-sulfo-3-O-sulfoglucosamine and 2-O-sulfoglucuronic acid.Glycoconjugate journal · 2020Article
- Identification of Protein Recognition Elements within Heparin Chains Using Enzymatic Foot-Printing in Solution and Online SEC/MS.Analytical chemistry · 2020Article
- The molecular basis of endolytic activity of a multidomain alginate lyase fromThe Journal of biological chemistry · 2019Article
- Updates to the Symbol Nomenclature for Glycans guidelines.Glycobiology · 2019Article
- Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR) Spectroscopy.Molecules (Basel, Switzerland) · 2018Review
- Analysis of sulfates on low molecular weight heparin using mass spectrometry: structural characterization of enoxaparin.Expert review of proteomics · 2018Review
- Synthetic Oligosaccharide Libraries and Microarray Technology: A Powerful Combination for the Success of Current Glycosaminoglycan Interactomics.ChemMedChem · 2018Review
- The Sea as a Rich Source of Structurally Unique Glycosaminoglycans and Mimetics.Microorganisms · 2017Review
- Structural Analysis of Heparin-Derived 3-O-Sulfated Tetrasaccharides: Antithrombin Binding Site Variants.Journal of pharmaceutical sciences · 2017Article
- Conformational flexibility of PL12 family heparinases: structure and substrate specificity of heparinase III from Bacteroides thetaiotaomicron (BT4657).Glycobiology · 2017Article
- Engineering broad-spectrum digestion of polyuronides from an exolytic polysaccharide lyase.Biotechnology for biofuels · 2016Article
- A Surface Loop in the N-Terminal Domain ofJournal of applied glycoscience · 2016Article
- Docking server for the identification of heparin binding sites on proteins.Journal of chemical information and modeling · 2014Article
- Insight into the role of substrate-binding residues in conferring substrate specificity for the multifunctional polysaccharide lyase Smlt1473.The Journal of biological chemistry · 2014Article
- A polysaccharide lyase from Stenotrophomonas maltophilia with a unique, pH-regulated substrate specificity.The Journal of biological chemistry · 2014Article
- The solution structure of heparan sulfate differs from that of heparin: implications for function.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Heparinase II (HepII) is an 85-kDa dimeric enzyme that depolymerizes both heparin and heparan sulfate glycosaminoglycans through a beta-elimination mechanism. Recently, we determined the crystal structure of HepII from Pedobacter heparinus (previously known as Flavobacterium heparinum) in complex with a heparin disaccharide product, and identified the location of its active site. Here we present the structure of HepII complexed with a heparan sulfate disaccharide product, proving that the same binding/active site is responsible for the degradation of both uronic acid epimers containing substrates. The key enzymatic step involves removal of a proton from the C5 carbon (a chiral center) of the uronic acid, posing a topological challenge to abstract the proton from either side of the ring in a single active site. We have identified three potential active site residues equidistant from C5 and located on both sides of the uronate product and determined their role in catalysis using a set of defined tetrasaccharide substrates. HepII H202A/Y257A mutant lost activity for both substrates and we determined its crystal structure complexed with a heparan sulfate-derived tetrasaccharide. Based on kinetic characterization of various mutants and the structure of the enzyme-substrate complex we propose residues participating in catalysis and their specific roles.
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