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