We are interested in the Structure-Guided Development of:

• anticancer agents targeting DNA lesion repair and de novo nucleotide biosynthesis pathways
• modulators that inhibit or enhance the incorporation of non-natural nucleotides into DNA or RNA
• antidiabetic agents/biomarkers targeting glucose sensing transcription factors
• antibacterial/antiviral agents targeting DNA repair/bypass and nucleotide metabolism

 

We utilize various tools including X-ray crystallography, Biochemical/biophysical assays, and Cell biology to investigate the target pathways/enzymes to develop novel inhibitors or modulators.

 

Project 1.  Structural/biochemical study on the repair and bypass of DNA lesions along with de novo nucleotide biosynthesis for tackling cancer

Fig 1.  Brief scheme of base excision repair (BER) and one of the enzymes involved in BER, MBD4, and its mechanism of action.

 

Fig 2.  De novo biosynthesis of AMP and GMP from IMP, and one of the glycosylases (AAG) and its reaction mechanism.

 

 

Project 2.  Structural and biochemical studies of ChREBP (Carbohydrate Responsive Element Binding Protein) and its binding partners controlling glucose homeostasis for Treating diabetes

 

Fig 3.  ChREBP and its domains with the amino acid sequence of N-terminal NLS domain. The binding partners of ChREBP, 14-3-3 and importin-α, are crucial for its nuclear localization.

 

 

Project 3.  Structure-based drug discovery for broad-spectrum inhibitors to fight infectious diseases

Fig 4.  Schematic diagram of folate cycle and one of its enzyme serine hydroxymethyltransferase (SHMT). Human and Sa SHMT are superposed to show the structural difference that could be targeted.

 

Fig 5.  Schematic diagram of glyoxylate shunt and two of its enzymes, malate synthase (MS) and isocitrate lyase (ICL) along with some of the potential scaffold that could be used for structural modification.