title: Effector sites in the three-dimensional structure of mammalian sperm beta-acrosin.
abstract: BACKGROUND
  Proacrosin is a serine protease found specifically within the acrosomal vesicle of all mammalian spermatozoa. During fertilization proacrosin autoactivates to form beta-acrosin, in which there is a "light" chain cross-linked to a "heavy" chain by two disulphide bonds. beta-acrosin is thought to be multifunctional with roles in acrosomal exocytosis, as a receptor for zona pellucida proteins, and as a protease to facilitate penetration of spermatozoa into the egg.
  
  
  RESULTS
  The crystal structures of both ram and boar beta-acrosins have been solved in complex with p-aminobenzamidine to 2.1 A and 2.9 A resolution, respectively. Both enzymes comprise a heavy chain with structural homology to trypsin, and a light chain covalently associated in a similar manner to blood coagulation enzymes. In crystals of boar beta-acrosin, the carboxyl terminus of the heavy chain is inserted into the active site of the neighboring molecule. In both enzyme structures, there are distinctive positively charged surface "patches" close to the active site, which associate with carbohydrate from adjacent molecules and also bind sulfate ions.
  
  
  CONCLUSIONS
  From the three-dimensional structure of beta-acrosin, two separate effector sites are evident. First, proteolytic activity, believed to be important at various stages during fertilization, arises from the trypsin-like active site. Activity of this site may be autoregulated through intermolecular associations. Second, positively charged regions on the surface adjacent to the active site may act as receptors for binding zona pellucida glycoproteins. The spatial proximity of these two effector sites suggests there may be synergy between them.
authors.affiliation: Department of Biochemistry University of Bristol BS8 1TD, Bristol, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Tranter
authors.forename: J A
authors.initials: JA
authors.lastname: Read
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: R L
authors.initials: RL
authors.lastname: Brady
mesh_terms: D000176:Acrosin / Q000737:chemistry*; D000177:Acrosome / Q000201:enzymology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004527:Egg Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D000072216:Zona Pellucida Glycoproteins
chemical_list: D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D000072216:Zona Pellucida Glycoproteins; D000176:Acrosin