AMINO-ACID-SEQUENCE AND 3-DIMENSIONAL STRUCTURE OF THE STAPHYLOCOCCUS-AUREUS METALLOPROTEINASE AT 1.72 ANGSTROM RESOLUTION

Background: Aureolysin is an extracellular zinc-dependent metalloprote inase from the pathogenic bacterium Staphylococcus aureus, This enzyme exhibits in vitro activity against several molecules of biological si gnificance for the host, indicating that it is involved in the patholo gy of staphylococcal diseases. Results: Here we report the amino-acid sequence and inhibitor-free X-ray crystal structure of aureolysin, a m ember of the thermolysin family of zinc-dependent metalloproteinases. This enzyme, which binds one zinc and three calcium ions, comprises a single chain of 301 amino acids that consists of a beta-strand-rich up per domain and an alpha-helix-rich lower domain. Conclusions: The over all structure of aureolysin is very similar to that of the other three members of this family whose structures are known - thermolysin (TLN) from Bacillus thermoproteolyticus, neutral protease (NP) from Bacillu s cereus and elastase (PAE) from Pseudomonas aeruginosa, But an import ant difference has been encountered: in contrast to what has been obse rved in the other three members of this family (TLN, NP and PAE), inhi bitor-free aureolysin displays a 'closed' active site cleft conformati on. This new structure therefore raises questions about the universali ty of the hinge-bending motion model for the neutral metalloproteinase s.