Staphylococcus aureus SAUGI is a DNA mimic protein that targets Uracil-DNA glycosylase (UDG) in a wide range of species. In our previous work, we compared the binding affinity and inhibitory effects of SAUGI on five UDGs from S. aureus (SA), Mycobacterium tuberculosis (TB), human, Epstein–Barr virus (EBV) and Herpes simplex virus (HSV). Our results showed that SAUGI had the greatest inhibitory activity on the two viral UDGs, followed by SAUDG and human UDG, and had almost no effect on TBUDG. Subsequently, further structure-based protein engineering was used to modulate the inhibitory strength of SAUGI on human UDG and HSVUDG. Our results showed that the differential inhibitory effects can be successfully modulated, and suggested possible application of the SAUGI mutant proteins to HSV-related studies. To date, only two functional studies of SAUGI had been reported, and much more research needs to be performed in this field. Here, we aim to extend our knowledge of SAUGI and to discover its potential applications. We will focus on three topics: (1) Following the previous findings to further investigate the differential inhibiting strength of SAUGI on different UDGs by analyzing the complex structures, (2) Evaluating if SAUGI can be used as a competitive inhibitor of HIV Vpr (Human immunodeficiency virus Viral protein R), and (3) Discovering small molecule drugs of SAUGI for potential application on MRSA (Methicillin-resistant Staphylococcus aureus) study. We expect the results of this work will extend our understanding of DNA mimics in general, and it may also open a way for novel therapeutic applications for this kind of protein as well.
|Effective start/end date||8/1/17 → 7/31/18|
- DNA mimic protein
- Uracil-DNA glycosylase
- Staphylococcus aureus Uracil glycosylase inhibitor