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Quantitative biophysical life science(Chemistry)

Ohkubo TadayasuProfessor

The laboratory of biophysical chemistry aims to determine three-dimensional structures of proteins and their complexes in order to obtain novel structural insights into their functions. X-ray crystallography and NMR spectroscopy are conducted to define molecular structure at an atomic level. Intermolecular interactions, structural stability, complex formation, intramolecular dynamics and reaction kinetics are probed with various physico-chemical techniques including spectroscopic, hydrodynamic and thermodynamic analyses, i.e. circular dichroism, analytical ultra centrifugation, isothermal titration calorimetry, etc.

Research theme

Structure determination of proteins with X-ray crystallography and NMR spectroscopy.

Physico-chemical analysis on molecular properties and interactions of proteins.

Development of protein production systems for physico-chemical studies.

Protein dynamics analysis and drug discovery.

Representative achievements

"N-terminal HCV core protein fragment decreases 20S proteasome activity in the presence of PA28γ." Zheng Y, Shimamoto S, Maruno T, Kobayashi Y, Matsuura Y, Kawahara K, Yoshida T, Ohkubo T., Biochem Biophys Res Commun. (2019) 509, 590-595

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"Ordered self-assembly of the collagenous domain of adiponectin with noncovalent interactions via glycosylated lysine residues." Takuwa A, Yoshida T, Maruno T, Kawahara K, Mochizuki M, Nishiuchi Y, Kobayashi Y, Ohkubo T., FEBS Lett. (2016) 590, 195-201

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" Thermodynamic and NMR analyses of NADPH binding to lipocalin-type prostaglandin D synthase." Qin S, Shimamoto S, Maruno T, Kobayashi Y, Kawahara K, Yoshida Y, Ohkubo T., Biochem Biophys Res Commun. (2015) 468, 234-239

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"Structure of the CFA/III major pilin subunit CofA from human enterotoxigenic Escherichia coli determined at 0.90 Å resolution by sulfur-SAD phasing.", Fukakusa S, Kawahara K, Nakamura S, Iwashita T, Baba S, Nishimura M, Kobayashi Y, Honda T, Iida T, Taniguchi T, Ohkubo T., Acta Crystallogr D Biol Crystallogr. 68, 1418-1429, (2012)

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“Structure and Reaction Mechanism of Human Nicotinamide Phosphoribosyltransferase.” Takahashi R, Nakamura S, Nakazawa T, Minoura K, Yoshida T, Nishi Y, Kobayashi Y, Ohkubo, T., J. Biochem., 147, 95-107, (2010)

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“NMR solution structure of lipocalin-type prostaglandin D synthase: Evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the central cavity”, Shimamoto S, Yoshida T, Inui T, Gohda K, Kobayashi Y, Fujimori K, Tsurumura T, Aritake K, Urade Y, Ohkubo, T., J. Biol. Chem., 282, 31373-31379, (2007)

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“Apo- and holo-structures of 3alpha-hydroxysteroid dehydrogenase from Pseudomonas sp. B-0831. Loop-helix transition induced by coenzyme binding.”, Nakamura S, Oda M, Kataoka S, Ueda S, Uchiyama S, Yoshida T, Kobayashi Y, Ohkubo, T., J Biol Chem., 281, 31876-31884, (2006)

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“Structure of cytochrome c552 from a moderate thermophilic bacterium, Hydrogenophilus thermoluteolus: comparative study on the thermostability of cytochrome c.”, Nakamura S, Ichiki S, Takashima H, Uchiyama S, Hasegawa J, Kobayashi Y, Sambongi Y, Ohkubo, T., Biochemistry, 45, 6115-6123, (2006)

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"Solution structure of an extracelluar domain containing the WSxWS motif of the granulocyte colony-stimulating factor receptor and its interaction with ligand ", Yamasaki, K., Naito, S., Anaguchi, H., Ohkubo, T., and Ota, Y., Nat. Struct. Biol., 4, 498-504 (1997)

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"Methylation dependent functional switch mechanism newly found in the Escherichia coli Ada protein", Ohkubo, T., Sakashita, H., Sakuma, T., Kainosho, M., Sekiguchi, M., and Morikawa, K., J. Am. Chem. Soc., 116, 6035-6036, (1994)

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