• Laboratory of Biopharmaceutics
• Laboratory of Applied Phrmacology
• Laboratory of Biorecognition Chemistry
• Laboratory of Cancer Cell Biology
• Laboratory of Chemical Biology
• Laboratory of Synthetic and
  Medicinal Chemistry
• Laboratory of Molecular Neurobiology
• Laboratory of Gene Regulation
• Laboratory of Molecular Cell Biology
• Laboratory of Medicinal Bioresources
• Laboratory of Synthetic and Biomolecular Organic Chemistry
• Laboratory of Biointerface Chemistry
• Laboratory of Structual Biology
• Laboratory of Phrmaceutical Physiology
• Laboratory of Medical Pharmaceutics
  Laboratory of Community Pharmacy
• Laboratory of Plant Resource Sciences
• Laboratory of Clinical Pharmacology
• Laboratory of Clinical Pharmacokinetics
• Laboratory of Pharmaceutical Therapy
  and Neuropharmacology
• Department of Hospital Pharmacy
• Department of Pharmaceutical Technology
• Division of Pharmacognosy
• Division of Natural Products Chemistry
• Division of Kampo-Pharmaceutics
• Division of Medicinal Pharmacology
• Division of Pathogenic Biochemistry
• Division of Gastrointestinal Pathophysiology
• Division of Neuromedical Science
• Division of Nutritional Biochemistry
• Division of Kampo Diagnostics
• Division of Natural Drug Discovery
• Molecular Genetics Research Laboratory, Life Science Research Center

In the living organism, a protein molecule folds into its three-dimensional structure that is encoded in its sequence. Since the function of a protein is closely linked to its structure, experimental determination of the protein structure is a matter of high importance. We are using nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography to study the protein structures.

The aim of our study is to understand the structure and function of proteins which are fundamentally important in disease onset and progression. Under some conditions, proteins fail to fold correctly, or to remain correctly folded, and this failure can result in a wide range of diseases. One group of diseases, known as amyloidoses, which includes familial amyloid polyneuropathy and spinocerebellar ataxia, involves the deposition of misfolded proteins in a variety of organs such as liver, heart and brain. Amyloid fibrils have been the target of increasing attention because of their central role in several human pathologies, including Alzheimer's disease and transthyretin-related amyloidosis. Our research interests also center on the structural bases for the formation of amyloid fibrils by transthyretin using a combination of neutron crystallography, X-ray crystallography and biochemical methods. In particular, neutron protein crystallography is an experimental method of directly locating H atoms that are essential in enzymatic function and molecular recognition. Targets for these studies include important proteins in the treatment of amyloidosis, osteoporosis and other disease states.

Another aim of our study is to understand the molecular machinery of ESCRT (Endosomal Sorting Complex Required for Transport) system in cell division at atomic level using X-ray crystallography, NMR and other methods. We have shown that ESCRT complex are conserved in archaea (crenarchaea), and have an important role in cell division.

The sequenced genomes of hyperthermophilic crenarchaeotes lack genes for members of the FtsZ/tubulin and MreB/actin superfamilies of cell division proteins. The absence of orthologs of these proteins in archaea (crenarchaea) has prompted us to attempt to identify the archaeal cell division machinery. Most hyperthermophilic crenarchaea encode homologs of ESCRT-III components and the adenosine triphosphatase (ATPase) Vps4. However, no homologs of the ESCRT-0, -I, or -II systems are apparent. We have determined the crystal structure of archaeal Vps4 in a complex with ESCRT-III (Science, 2008), and showed that the archaeal ESCRT system plays a key role in cell division. The Vps4 and ESCRT-III genes are within an operon structure with the third protein, CdvA, indicating that these three genes are functionary related. Currently, we are focusing on CdvA protein to clarify the functions.