title: Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer.
abstract: Human platelet heparanase has been purified to homogeneity and shown to consist of two, non-covalently associated polypeptide chains of molecular masses 50 and 8 kDa. Protein sequencing provided the basis for determination of the full-length cDNA for this novel protein. Based upon this information and results from protein analysis and mass spectrometry, we propose a scheme to define the structural organization of heparanase in relation to its precursor forms, proheparanase and pre-proheparanase. The 8- and 50-kDa chains which make up the active enzyme reside, respectively, at the NH(2)- and COOH-terminal regions of the inactive precursor, proheparanase. The heparanase heterodimer is produced by excision and loss of an internal linking segment. This paper is the first to suggest that human heparanase is a two-chain enzyme.
authors.affiliation: Protein Science Research Operations, Kalamazoo, Michigan 49001, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Fairbanks
authors.forename: A M
authors.initials: AM
authors.lastname: Mildner
authors.forename: J W
authors.initials: JW
authors.lastname: Leone
authors.forename: G S
authors.initials: GS
authors.lastname: Cavey
authors.forename: W R
authors.initials: WR
authors.lastname: Mathews
authors.forename: R F
authors.initials: RF
authors.lastname: Drong
authors.forename: J L
authors.initials: JL
authors.lastname: Slightom
authors.forename: M J
authors.initials: MJ
authors.lastname: Bienkowski
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: C A
authors.initials: CA
authors.lastname: Bannow
authors.forename: R L
authors.initials: RL
authors.lastname: Heinrikson
mesh_terms: D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary; D019281:Dimerization; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005966:Glucuronidase; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000099175:Heparanase
chemical_list: D018076:DNA, Complementary; D004792:Enzyme Precursors; D005966:Glucuronidase; D006026:Glycoside Hydrolases; D000099175:Heparanase