Amino-acid sequence and three-dimensional structure of the Staphylococcus aureus metalloproteinase at 1.72 A resolution.
BACKGROUND
Aureolysin is an extracellular zinc-dependent metalloproteinase from the pathogenic bacterium Staphylococcus aureus. This enzyme exhibits in vitro activity against several molecules of biological significance for the host, indicating that it is involved in the pathology of staphylococcal diseases.


RESULTS
Here we report the amino-acid sequence and inhibitor-free X-ray crystal structure of aureolysin, a member 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 upper domain and an alpha-helix-rich lower domain.


CONCLUSIONS
The overall 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 Bacillus cereus and elastase (PAE) from Pseudomonas aeruginosa. But an important difference has been encountered: in contrast to what has been observed in the other three members of this family (TLN, NP and PAE), inhibitor-free aureolysin displays a 'closed' active site cleft conformation. This new structure therefore raises questions about the universality of the hinge-bending motion model for the neutral metalloproteinases.
Banbula
A
A
Jagiellonian University Institute of Molecular Biology Al. Mickiewicza 3, 31-120, Krakow, Poland.
Potempa
J
J
Travis
J
J
Fernandez-Catalán
C
C
Mann
K
K
Huber
R
R
Bode
W
W
Medrano
F
F
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000201:enzymology*; D055672:Static Electricity; D013379:Substrate Specificity; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D008666:Metalloendopeptidases; C115504:aureolysin; D015032:Zinc; D002118:Calcium