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Alexey Eroshkin

Publications and source records attributed to Alexey Eroshkin.

2 recordsLinked to original sources

CutDB: a proteolytic event database.

Beyond the well-known role of proteolytic machinery in protein degradation and turnover, many specialized proteases play a key role in various regulatory processes. Thousands of highly specific proteolytic events are associated with normal and pathological conditions, including bacterial and viral infections. However, the information about individual proteolytic events is dispersed over multiple publications and is not easily available for large-scale analysis. CutDB is one of the first systematic efforts to build an easily accessible collection of documented proteolytic events for natural proteins in vivo or in vitro. A CutDB entry is defined by a unique combination of these three attributes: protease, protein substrate and cleavage site. Currently, CutDB integrates 3070 proteolytic events for 470 different proteases captured from public archives (such as MEROPS and HPRD) and publications. CutDB supports various types of data searches and displays, including clickable network diagrams. Most importantly, CutDB is a community annotation resource based on a Wikipedia approach, providing a convenient user interface to input new data online. A recent contribution of 568 proteolytic events by several experts in the field of matrix metallopeptidases suggests that this approach will significantly accelerate the development of CutDB content. CutDB is publicly available at http://cutdb.burnham.org.

Animals↗

Streptococcal mitogenic exotoxin, SmeZ, is the most susceptible M1T1 streptococcal superantigen to degradation by the streptococcal cysteine protease, SpeB.

Superantigens (SAgs) play an important role in the pathogenesis of severe invasive infections caused by Group A Streptococcus (GAS). We had shown earlier that the expression of streptococcal cysteine protease SpeB results in partial loss of the immune-stimulating activity of the native secreted GAS SAgs, namely the streptococcal pyrogenic exotoxins produced by the globally disseminated M1T1 GAS strain, associated with invasive infections worldwide. In this study, we examined the susceptibility of each of the M1T1 recombinant SAgs to degradation by rSpeB. Whereas SmeZ was degraded completely within 30 min of incubation with rSpeB, SpeG, and SpeA were more resistant and SpeJ was completely unaffected by the proteolytic effects of this protease. Proteomic analyses demonstrated that the order of susceptibility of the M1T1 SAgs to SpeB proteolysis is unaltered when they are present in a mixture that reflects their native physiological status. As expected, the degradation of SmeZ abolished its immune stimulatory activity. In silico sequence disorder and structural analyses revealed that SmeZ, unlike the three other structurally related SAgs, possesses a putative SpeB cleavage site within an area of the protein likely to be exposed to the surface. The study provides evidence for the effect of subtle structural differences between highly similar SAgs on their biological activity.

Amino Acid Sequence↗