2PE4

Structure of Human Hyaluronidase 1, a Hyaluronan Hydrolyzing Enzyme Involved in Tumor Growth and Angiogenesis

Summary for 2PE4

• Entry DOI: 10.2210/pdb2pe4/pdb
• Descriptor: Hyaluronidase-1, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: hyaluronidase, hyaluronan, egf-like domain, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : Q12794
• Total number of polymer chains: 1
• Total formula weight: 49417.18

Authors

Chao, K.L.,Herzberg, O. (deposition date: 2007-04-02, release date: 2007-06-12, Last modification date: 2024-10-30)

Primary citation

Chao, K.L.,Muthukumar, L.,Herzberg, O.
Structure of Human Hyaluronidase-1, a Hyaluronan Hydrolyzing Enzyme Involved in Tumor Growth and Angiogenesis
Biochemistry, 46:6911-6920, 2007

PubMed 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.

PubMed: 17503783
DOI: 10.1021/bi700382g

Experimental method

X-RAY DIFFRACTION (2 Å)