![fa-400-12-x-p cad fa-400-12-x-p cad](https://2.bp.blogspot.com/-XQUdSAsdr4U/UNLDoXwMcJI/AAAAAAAADHQ/ESHEWL_pF3M/s1600/свойства+клеммы3.jpg)
With structurally related metalloproteases contributing to virulence of diverse genera of bacteria, it may be necessary to tailor the zymogen activation mechanism to suit the physiology and virulence strategy of each pathogen. As with the role of Aur in activating proSspA, other M4 metalloproteases in diverse genera of pathogenic bacteria also function like proprotein convertases, including activation of cholera toxin by the Vibrio haemagglutinin metalloprotease ( Booth et al., 1984), activation of Clostridium perfringens epsilon- and iota-toxins by the lambda-toxin metalloprotease ( Jin et al., 1996 Minami et al., 1997 Gibert et al., 2000), activation of phospholipase C by the Mpl metalloprotease of Listeria ( Poyart et al., 1993 Marquis et al., 1997) and activation of the Enterococcus faecalis SprE serine protease by GelE, which is coexpressed in an operon with SprE ( Qin et al., 2000 Kawalec et al., 2005). Aur is structurally similar to the zinc metalloprotease thermolysin ( Banbula et al., 1998), and both belong to the M4 family of metallopeptidases ( Rawlings and Barrett, 1995 Rawlings et al., 2006), which typically undergo autocatalytic activation ( McIver et al., 1993 Marie-Claire et al., 1998 Kooi et al., 2005 2006). Although proSspA exhibited autocatalytic cleavage of glutamine residues in its NTP, this was not sufficient for activation, which required additional Aur-dependent processing at Leu 58 and Val 69 ( Nickerson et al., 2007).
![fa-400-12-x-p cad fa-400-12-x-p cad](https://static.cambridge.org/binary/version/id/urn:cambridge.org:id:binary:20200904112413925-0126:S0884291420000709:S0884291420000709_fig6.png)
The initiating protease in the staphylococcal proteolytic cascade (SPC) would have to undergo autocatalytic activation. Expression of SspA and SspB, as well as a metalloprotease aureolysin (Aur), also occurred rapidly upon uptake of hyper-virulent Community-Acquired Methicillin resistant Staphylococcus aureus by human neutrophils, alluding to a role in modifying the vacuole compartment ( Burlak et al., 2007).
Fa 400 12 x p cad Activator#
Mature SspB cleaved arginine residues in fibrinogen, fibronectin and kininogen at sites recognized by the respective plasma serine proteases plasmin, plasminogen activator and kallikrein ( Massimi et al., 2002). We proposed that S. aureus emulates the environment in which it thrives, by using a proteolytic cascade to moderate adhesion and invasion ( McGavin et al., 1997 Rice et al., 2001 Massimi et al., 2002), as evident from the rapid degradation of cell-surface fibronectin-binding proteins by the SspA serine protease ( Rice et al., 2001), which is coexpressed in an operon with a cysteine protease SspB, and is needed to activate proSspB ( Massimi et al., 2002). Each precursor is activated when its propeptide is removed, in turn activating another precursor in a sequential cascade. Proteins that participate in these pathways typically circulate as inactive precursors with N-terminal propeptides (NTP) and C-terminal serine protease domains ( Spronk et al., 2003). We conclude that the FTP domain of proAur is adapted to facilitate a rapid autocatalytic activation mechanism, consistent with the role or proAur as initiator of the staphylococcal proteolytic cascade.Īs a leading cause of nosocomial bacteraemia and metastatic infection, Staphylococcus aureus specializes in manipulating plasma proteins in the coagulation, complement and contact activation pathways ( Patti et al., 1994 Massimi et al., 2002 Chavakis et al., 2005 Imamura et al., 2005 Nizet, 2007). Consequently, this segment of the FTP domain promotes intramolecular processing of proAur while bestowing a chaperone function, but discourages processing within the FTP domain of proElastase, where activation must be co-ordinated with passage across a second membrane. When TL 86 in the FTP domain was replaced with RY, an intact N-terminal propeptide was secreted, but the M4 metalloprotease domain was degraded. This differed from the mechanism described for proElastase, where the FTP domain has an RY motif in place of TL 86, and processing occurred at the junction of the propeptide and metalloprotease domains, which remained as an inactive complex during passage across the outer membrane. Autocatalytic activation of proAur was initiated by processing at T85↓L 86 in the FTP domain. As with other M4 metalloproteases, including elastase of Pseudomonas aeruginosa, the propeptide of proAur contains an N-terminal fungalysin-thermolysin-propeptide (FTP) domain. The Staphylococcus aureus proteolytic cascade consists of a metalloprotease aureolysin (Aur), which activates a serine protease zymogen proSspA, which in turn activates the SspB cysteine protease.