Sakurako Shimotakahara

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alpha-Synuclein is the major component of the filamentous Lewy bodies and Lewy-related neurites, neuropathological hallmarks of Parkinson's disease. Although numerous studies on alpha-synuclein fibrillation have been reported, the molecular mechanisms of aggregation and fibrillation at the initial stage are still unclear. In the present study, structural(More)
One of the most well known characteristics for Parkinson's disease (PD) is a polymerization of wild-type or mutant alpha-synuclein into aggregates and fibrils, commonly observed as Lewy bodies and Lewy neuritis in PD patients. Although numerous studies on alpha-synuclein fibrillation have been reported, the molecular mechanisms of aggregation and(More)
Hho1p is assumed to serve as a linker histone in Saccharomyces cerevisiae and, notably, it possesses two putative globular domains, designated HD1 (residues 41-118) and HD2 (residues 171-252), that are homologous to histone H5 from chicken erythrocytes. We have determined the three-dimensional structure of globular domain HD1 with high precision by(More)
A structural characterization of bound water molecules in ribonuclease T1 (RNase T1) was carried out by nuclear magnetic resonance spectroscopy and molecular dynamics simulation. Amide protons of residues Trp59, Leu62, Tyr68 and Phe100 were found to cross-relax with protons of bound waters. Molecular dynamics simulations of the 120 water molecules observed(More)
Water ligand observed via gradient spectroscopy (WaterLOGSY), saturation transfer difference and NOE pumping NMR techniques were used to identify ligand binding with a receptor. Although these experiments were originally designed to observe ligands in complexes, their application is limited by the affinity of ligands towards target molecules. Here the(More)
WaterLOGSY and STD experiments are widely used as NMR-based screening techniques in drug research. In the present study, an improved STD pulse sequence was developed, and its efficiency and applicability of observing the ligand signals were evaluated compared with the WaterLOGSY experiment. A combination of presaturation, a WET sequence and subsequent(More)
A difference diffusion-based NMR technique and cold-spray ionization mass spectrometry were employed as a solution-based approach for identifying a ligand binding with a protein receptor. The difference diffusion-based NMR technique, called difference NOE-pumping, can directly detect the ligand interacting with a protein receptor. This technique uses a(More)
Phospholipase C (PLC) plays an important role in intracellular signal transduction by hydrolyzing phosphatidylinositol 4,5-bis-phosphate, a membrane phospholipid. Currently, thirteen mammalian PLC isozymes have been identified, which are divided into six classes on the basis of structure and mechanisms. All the PLC isozymes share common domains including(More)
Translational motions of water molecules in various systems equilibrated at room temperature are thought to be diffusive and nondirectional. We performed molecular dynamics simulations of a protein system and showed that the water molecules collectively move around the protein. The motions of two water molecules, which were about 12 A away from each other,(More)