title: Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis.
abstract: Human hyaluronidases (Hyals) are a group of five endo-beta-acetyl-hexosaminidase enzymes, Hyal-1, -2, -3, -4, and PH-20, which degrade hyaluronan using a hydrolytic mechanism of action. Catalysis by these Hyals has been shown to follow a double-displacement scheme. This involves a single Glu residue within the enzyme, the only catalytic residue, as the proton donor (acid). Also involved is a carbonyl group of the hyaluronan (HA) N-acetyl-D-glucosamine as a unique type of nucleophile. Thus the substrate participates in the mechanism of action of its own catalysis. An oxocarbonium ion transition state is postulated, but there is no formation of a covalent enzyme-glycan intermediate, as found in most such reactions. The major domain is catalytic and has a distorted (beta/alpha)8 triose phosphate isomerase (TIM) barrel fold. The C-terminal domain is separated by a peptide linker. Each Hyal has a different C-terminal sequence and structure, the function of which is unknown. These unique C-termini may participate in the additional function(s) associated with these multifunctional enzymes.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Jedrzejas
authors.forename: Robert
authors.initials: R
authors.lastname: Stern
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase