title: Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis.
abstract: Mammalian hyaluronidases hydrolyze hyaluronan, a polysaccharide of diverse physiological roles found in all tissues and body fluids. In addition to its function in normal cellular hyaluronan turnover, human hyaluronidase-1 is implicated in cancer proliferation, angiogenesis, and inflammatory diseases; its expression is up-regulated in advanced stages of bladder cancer, whereas the expression of the alternative splice-variants is down-regulated. The crystal structure reveals a molecule composed of two closely associated domains: a catalytic domain that adopts a distorted (beta/alpha)8 barrel resembling that of bee venom hyaluronidase, and a novel, EGF-like domain, characteristic of involvement in protein-protein interactions and regulatory processes. The structure shows that the fold of this unique EGF-like domain is intact in four alternative splice-variants, whereas the catalytic domain is likely to be unfolded. Thus, these variants may function by competing with the full-length enzyme for the putative protein partner and regulating enzymatic activity in healthy cells.
authors.affiliation: Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.
authors.forename: Kinlin L
authors.initials: KL
authors.lastname: Chao
authors.forename: Lavanya
authors.initials: L
authors.lastname: Muthukumar
authors.forename: Osnat
authors.initials: O
authors.lastname: Herzberg
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D014644:Genetic Variation; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D006821:Hyaluronoglucosaminidase