Structural biology is the science to understand the biological phenomena by structure analyses. Since the function of a protein depends on its structure, analyzing three-dimensional structure at atomic resolution is essential for answering many emerging questions in biomedical sciences. However, nowadays, structural elucidation of any particular protein is the just starting point of structure-function study of target protein. Structural information will be combined with various functional studies to draw clear picture of biomedical phenomenon.

Our ongoing research projects include several proteins involved in protein kinesis, signal transduction and microbial pathogenesis. These issues have been received extensive attention as the major questions of current biology and because of their biomedical relevance. In addition to the major research areas, we have established collaborative relationship with some of leading research groups around the world. Furthermore, structural information could be used for developing a novel drug for life-threaten human disease, and for developing a novel nanomaterial or nanodevice which would have the potential applications in nanotechnology and biotechnology.

1. Protein kinesis

Protein kinesis concerns the area of protein turn over, modification and quality control.

Protein quality control is essential for cell viability by maintaining the proper function of proteins as well as degrading aggregates of denatured proteins. Quality control is mediated by molecular chaperones, convertases and proteases which act to control the folding, activation and degradation of proteins in the cell. Currently we are working on several proteases and heat shock proteins with an aim to understand the mechanism of the functional regulation and recognition specificity of them.

Conjugation and deconjugation of the ubiquitin or ubiquitin-like protein (UBL) to the substrate proteins turn out to be the major actions for controlling the protein quality and altering the function of the proteins. Consequently abnormal function of this system causes many human diseases including cancers and metabolic diseases. In this aspect, structural studies of UBL ligases and hydrolases, which are the major players in this process, are necessary for understating the molecular mechanism of their actions and pathogeneses of the disease. Ultimately, structural information will be used for the development of novel inhibiters which can control the abnormal cellular process mediated by UBL-controlled proteins. In this project, we are interested in the structural understanding of substrate selectivity of UBL-ligases and hydrolases.

2. Signaling at the cell membrane
Transmission of the environmental signals to inside of the cell regulates various cellular responses such as immune reaction, cell growth and division. We are focusing on the structural analyses of the ligand-receptor interaction which occurs on the plasma membrane as an initial step of various cellular responses. In addition, we also have an interest on the structural elucidation of the membrane proteins which have a role in singling or transporting foreign molecules through the plasma membrane.

3. Microbial pathogenesis
The structural elucidation of the pathogenesis of the infectious disease caused by bacteria and virus are the major interest in my laboratory since that could be the starting point for the structure-based development of novel antibacterial or antiviral drug candidates. Current projects deal with the quorum sensing and two-component systems in bacteria and the proteins in Herpes viruses. In addition, structural proteomics studies of several pathogenic bacteria are on the progress.

4. Z-DNA biology

Left-handed Z-DNA is a higher energy form of the double helix, stabilized by negative supercoiling generated by transcription or unwrapping nucleosomes. Z-DNA is also stabilized by specific protein binding; Z-DNA binding proteins. It is revealed that Z-DNA or Z-DNA binding proteins has a critical roles in transcription, chromatin remodeling, innate immune system and viral infection. We are currently working on structural and functional identification of various Z-DNA binding proteins and their roles in the cells.

5. Bionanotechnology & synthetic biology

Bionanotechnology, an emerging field in nanotechnology, uses concepts from chemistry, biochemistry, and molecular biology for the construction of novel nanomaterials and nonodevices using biological materials. This project includes (1) production of the supramolecular assemblies, molecular switches, nanobio conjugate and other nano-sized biomaterials (2) examination of their structure and characteristics and (3) application of these molecules for a nanodevice, nanomaterial and nanobiomedicine. Furthermore, this technology can be applied to a design or synthesis of a novel system including cellular and signaling networks or synthetic living organism using the biological materials as the parts.