|Title||Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Chao, KL, Muthukumar, L, Herzberg, O|
|Date Published||2007 Jun 12|
|Keywords||Amino Acid Sequence, Binding Sites, Conserved Sequence, Crystallography, X-Ray, Genetic Variation, Humans, Hyaluronoglucosaminidase, Models, Molecular, Molecular Sequence Data, Neoplasms, Neovascularization, Pathologic, Protein Conformation, Sequence Alignment, Sequence Homology, Amino Acid|
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.
|Grant List||P01-GM057890 / GM / NIGMS NIH HHS / United States|