2008 Fiscal Year Final Research Report
Analysis of oxygen activation mechanism in the heme-containing dioxygenases
Project/Area Number |
19770094
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Structural biochemistry
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Research Institution | The Institute of Physical and Chemical Research |
Principal Investigator |
SUGIMOTO Hiroshi The Institute of Physical and Chemical Research, 城生体金属科学研究室, 専任研究員 (90344043)
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Project Period (FY) |
2007 – 2008
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Keywords | ヘムタンパク質 / 共鳴ラマン分光 / X線結晶学 / トリプトファン |
Research Abstract |
2つのヘム含有二原子酸素添加酵素(IDO,TDO)の反応メカニズムを明らかにするために共鳴ラマン分光法によりIDOの反応中間体である酸素結合型の電子状態を明らかにした。また、IDO変異体の機能解析・X線結晶構造解析・共鳴ラマン分光解析により明らかにした活性中心のタンパク質残基の役割とDFT法による理論計算結果から、新しい反応スキームを提案した。さらに、TDOの協同的基質結合性とそのメカニズム明らかにした。
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[Journal Article] Cooperative binding of L-trp to human tryptophan 2,3-dioxygenase : resonance Raman spectroscopic analysis.2009
Author(s)
Fukumura, E., Sugimoto, H., Misumi, Y., Ogura, T., Shiro, Y.
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Journal Title
J. Biochem. 145
Pages: 505-515
Peer Reviewed
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[Journal Article] Structure-based design of a highly active vitamin D hydroxylase from Streptomyces griseolus CYP105A1.2008
Author(s)
Hayashi, K., Sugimoto, H., Shinkyo, R., Yamada, M., Ikeda, S., Ikushiro, S., Kamakura, M., Shiro, Y., Sakaki, T.
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Journal Title
Biochemistry 47
Pages: 11964-11972
Peer Reviewed
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[Journal Article] Density functional theory study on a missing piece in understanding of heme chemistry : the reaction mechanism for indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.2008
Author(s)
Chung, L. W., Li, X., Sugimoto, H., Shiro, Y., Morokuma, K.
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Journal Title
J. Am. Chem. Soc. 130
Pages: 12299-12309
Peer Reviewed
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[Journal Article] Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors.2008
Author(s)
Nakashima, H., Uto, Y., Nakata, E., Nagasawa, H., Ikkyu, K., Hiraoka, N., Nakashima, K., Sasaki, Y., Sugimoto, H., Shiro, Y., Hashimoto, T., Okamoto, Y., Asakawa, Y., Hori, H.
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Journal Title
Bioorg. Med. Chem. 16
Pages: 8661-8669
Peer Reviewed
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[Journal Article] Crystal structure of CYP105A1 (P450SU-1) in complex with 1alpha,25-dihydroxyvitamin D_3.2008
Author(s)
Sugimoto, H., Shinkyo, R., Hayashi, K., Yoneda, S., Yamada, M., Kamakura, M., Ikushiro, S., Shiro, Y., Sakaki, T.
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Journal Title
Biochemistry 47
Pages: 4017-4027
Peer Reviewed
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