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Literature summary for 3.2.1.166 extracted from

  • Gandhi, N.; Freeman, C.; Parish, C.; Mancera, R.
    Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans in glycoside hydrolase family 79 endo-D-glucuronidase (heparanase) (2012), Glycobiology, 22, 35-55.
    View publication on PubMed
Search for more literature for 3.2.1.166

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure analyses and homology modelling, overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
heparin heparin-binding domains HBD-1 and HBD-2 in heparanase, structure overview. The optimal length of a heparin chain required to bridge HBD-1 and HBD-2 for the effective inhibition is known to be an octadecasaccharide, whereas heparin tetrasaccharides and hexasaccharides as well as N-acetylated heparins (N-acetylation higher than 50%) are poor inhibitors of heparanase Homo sapiens
maltohexaose sulfate with at least 3 sulfate groups per internal sugar and up to four sulfates in the terminal sugar residues, docking sstudy and binding structure, overview Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
additional information the enzyme contains an N-terminal signal peptide, Met1-Ala35 Homo sapiens
-
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
8000
-
 1 * 50000, about, active form, + 1 * 8000, about, SDS-PAGE Homo sapiens
50000
-
 1 * 50000, about, active form, + 1 * 8000, about, SDS-PAGE Homo sapiens
65000
-
 1 * 65000, pro-form, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the enzyme is an endo-beta-glucuronidase that cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulfate oligosaccharides of appreciable size ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y251
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein the enzyme contains six N-glycosylation sites Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan reaction mechanism with transition states and glycosyl-enzyme intermediate, overview Homo sapiens
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the enzyme is an endo-beta-glucuronidase that cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulfate oligosaccharides of appreciable size Homo sapiens ?
-
 ?
additional information 6-O-sulfo heparosan and N-sulfo heparosan are resistant to cleavage by heparanase Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
heterodimer 1 * 50000, about, active form, + 1 * 8000, about, SDS-PAGE Homo sapiens
monomer 1 * 65000, pro-form, SDS-PAGE Homo sapiens
More human heparanase cDNA encodes the prepro-enzyme, which consists of 543 amino acid residues (65 kDa). Peptide cleavage of the prepro-enzyme at Ala35 generates the latent (pro-heparanase) 65 kDa heparanase. Proteolytic processing of the pro-enzyme removes a 6 kDa linker peptide (Ser110-Gln157), yielding an 8 kDa domain at the N-terminus (Gln36-Glu109) and a noncovalently linked 50 kDa catalytic domain with a lysine residue at the N-terminus (Lys158-Ile543). These two polypeptides form a heterodimer, which is the mature and active form of heparanase Homo sapiens

General Information

General Information Comment Organism
evolution the enzyme belongs to the glycoside hydrolase family 79, GH79 Homo sapiens
additional information the enzyme contains two glycosaminoglycan-binding domains. Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans, docked structures are used to propose a model for substrates and conformer selectivity based on the dimensions of the active site, homology modelling, overview. Molecular dynamics simulations. Conformations of docked pentasaccharides in the binding site of heparanase Homo sapiens
physiological function the enzyme is an endo-beta-glucuronidase associated with cell invasion in cancer metastasis, angiogenesis and inflammation. Cleaving heparan sulfate and releasing heparin/heparan sulfate oligosaccharides, the enzyme causes the release of growth factors, which accelerate tumor growth and metastasis Homo sapiens