小松 英幸 (コマツ ヒデユキ)

KOMATSU Hideyuki

写真a

職名

准教授

研究室住所

福岡県飯塚市川津680-4

研究分野・キーワード

タンパク質,糖鎖生物学,熱力学,酵素反応速度論

Scopus 論文情報  
総論文数: 0  総Citation: 0  h-index: 7

Citation Countは当該年に発表した論文の被引用数

取得学位 【 表示 / 非表示

  • 九州大学 -  博士(理学)  1993年03月

学内職務経歴 【 表示 / 非表示

  • 2019年04月
    -
    継続中

    九州工業大学   大学院情報工学研究院   生命化学情報工学研究系   准教授  

  • 2018年03月
    -
    2019年03月

    九州工業大学   大学院情報工学研究院   生命情報工学研究系   准教授  

所属学会・委員会 【 表示 / 非表示

  • 1993年04月
    -
    継続中
     

    日本生化学会  日本国

  • 1988年04月
    -
    継続中
     

    日本生物物理学会  日本国

専門分野(科研費分類) 【 表示 / 非表示

  • 生物物理学

 

論文 【 表示 / 非表示

  • Identification of a novel class of small compounds with anti-tuberculosis activity by in silico structure-based drug screening

    Taira J., Morita K., Kawashima S., Umei T., Baba H., Maruoka T., Komatsu H., Sakamoto H., Sacchettini J., Aoki S.

    Journal of Antibiotics    70 ( 11 ) 1057 - 1064   2017年11月  [査読有り]

     概要を見る

    © 2017 Japan Antibiotics Research Association All rights reserved. The enzymes responsible for biotin biosynthesis in mycobacteria have been considered as potential drug targets owing to the important role in infection and cell survival that the biotin synthetic pathway plays in Mycobacterium tuberculosis. Among the enzymes that comprise mycobacterium biotin biosynthesis systems, 7,8-diaminopelargonic acid synthase (DAPAS) plays an essential role during the stationary phase in bacterial growth. In this study, compounds that inhibit mycobacterial DAP AS were screened in the virtual chemical library using an in silico structure-based drug screening (SBDS) technique, and the antimycobacterial activity of the selected compounds was validated experimentally. The DOCK-GOLD programs utilized by in silico SBDS facilitated the identification of a compound, referred to as KMD6, with potent inhibitory effects on the growth of model mycobacteria (M. smegmatis). The subsequent compound search, which was based on the structural features of KMD6, resulted in identification of three additional active compounds, designated as KMDs3, KMDs9 and KMDs10. The inhibitory effect of these compounds was comparable to that of isoniazid, which is a first-line antituberculosis drug. The high antimycobacterial activity of KMD6, KMDs9 and KMDs10 was maintained on the experiment with M. tuberculosis. Of the active compounds identified, KMDs9 would be a promising pharmacophore, owing to its long-term antimycobacterial effect and lack of cytotoxicity.

    DOI Scopus

  • 2,3-Butandione 2-monoxime inhibits skeletal myosin II by accelerating ATP cleavage

    Komatsu H., Koseki Y., Kanno T., Aoki S., Kodama T.

    Biochemical and Biophysical Research Communications    490 ( 3 ) 849 - 854   2017年08月  [査読有り]

     概要を見る

    © 2017 Elsevier Inc. 2,3-Butandione 2-monoxime (BDM) is a widely used myosin inhibitor with an unclear mode of action. In this report, we investigated the mechanism of BDM oxime group nucleophilic reactivity on the phosphoester bond of ATP. BDM increased the ATPase activity of skeletal myosin subfragment 1 (S1) under conditions in which ATP cleavage is the rate-limiting step (K + , EDTA-ATPase activity of native S1 and Mg 2+ -ATPase activity of trinitrophenylated S1 and partially unfolded S1). Furthermore, the effect of BDM on the S1-bound adenosine 5′-(β,γ-imido) triphosphate (AMPPNP) 31 P NMR spectrum suggests that BDM changes the microenvironment around the phosphorus atoms of myosin-bound nucleotide. A computational search for the BDM-binding site in the adenosine 5′-[γ-thio] triphosphate (myosin–ATPγS) complex predicted that BDM is located adjacent to the nucleotide on myosin. Therefore, we propose that the BDM oxime group catalytically assists in ATP cleavage, thereby enhancing the ATPase activity of myosin in a manner analogous to pralidoxime-mediated reactivation of organophosphate-inactivated acetylcholinesterase. This is the first study suggesting that oxime provides catalytic assistance for ATP cleavage by an ATP-hydrolyzing enzyme.

    DOI Scopus

  • Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor

    Taira J., Kida Y., Inatomi K., Komatsu H., Higashimoto Y., Sakamoto H.

    Journal of Biochemistry    162 ( 2 ) 113 - 122   2017年08月  [査読有り]

     概要を見る

    © 2017 The Authors. Growth factor receptor-bound protein 14 (Grb14) is a negative regulator of insulin receptor (IR) and is involved in a negative feedback mechanism of insulin signaling. Grb14 associates with IR and inhibits its tyrosine kinase activity through the between pleckstrin homology and Src homology-2 (BPS) domain. We previously reported that the pharmacological inhibition and knockdown of glycogen synthase kinase-3 (GSK-3) facilitates the insulin-induced complex formation of human Grb14 (hGrb14) and IR, suggesting that GSK-3 suppresses hGrb14 recruitment to IR. This study further investigated a functional phosphorylation of the serine residues in hGrb14 BPS domain, identified as putative GSK-3 targets to verify an effect of GSK-3 on the hGrb14IR complex formation. In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser 358 , Ser 362 and Ser 366 ) and C-terminal (Ser 419 and Ser 423 ) regions of the BPS domain were phosphorylated by GSK-3. Coimmunoprecipitation and yeast two-hybrid (Y2H) experiments suggested that the negative charges genetically introduced on the Ser 358 , Ser 362 and Ser 366 suppressed the association of hGrb14 to IR. Surface plasmon resonance experiment gave Kd values of 8 nM for recombinant hGrb 14 with respect to the interaction with IR bsubunit, and this affinity was lost after the replacements of the Ser 358 , Ser 362 and Ser 366 with glutamic acid residues. Y2H experiment with the BPS domain alone; however, did not show any difference owing to the same mutations. It is therefore evident that the N-terminus of the BPS domain plays an important role in the regulation of hGrb14IR complex formation through phosphorylation, in addition to other domains.

    DOI Scopus

  • In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening

    Taira J., Ito T., Nakatani H., Umei T., Baba H., Kawashima S., Maruoka T., Komatsu H., Sakamoto H., Aoki S.

    International Journal of Mycobacteriology    6 ( 2 ) 142 - 148   2017年04月  [査読有り]

     概要を見る

    © 2017 The International Journal of Mycobacteriology. Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. Materials and Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS). Following the selection of such compounds, their antimycobacterial activity was examined. Results: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. Conclusion: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

    DOI Scopus

  • Development of a heme sensor using fluorescently labeled heme oxygenase-1

    Shinya Koga, Shun Yoshihara, Hiroki Bando, Kazuki Yamasaki, Yuichiro Higashimoto, Masato Noguchi, Shinji Sueda, Hideyuki Komatsu, Hiroshi Sakamoto

    Analytical Biochemistry    433 ( 1 ) 2 - 9   2013年02月  [査読有り]

    DOI Scopus

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著書 【 表示 / 非表示

  • 情報工学基礎実験 第2版

    九州工業大学情報工学部 情報工学基礎実験運営委員会編 ( 共著 )

    学術図書出版  2021年09月 ISBN: 9784780609448

     概要を見る

    情報工学基礎実験のテキストのフィジカルコンピューティングのセクションを改訂した。

  • 情報工学基礎実験

    小田部荘司,小松英幸,宮瀬紘平,李旻哲,清水文雄,許宗焄 ( 共編者 )

    学術図書出版社  2018年08月 ISBN: 978-4-7806-0664-5

  • A solvent model of nucleotide-protein interaction-partition coefficients of phosphates between water and organic solvent

    Komatsu H. ( 単著 )

      2018年05月 ISBN: 9789811084584

     概要を見る

    © Springer Nature Singapore Pte Ltd. 2018. In attempt to experimentally evaluate hydration/solvation of phosphoric compounds in aqueous solution, partitioning of phosphoric compounds from an aqueous solution to an organic solvent has been quantified. Transfer of phosphates from an aqueous solution into octanol was greatly enhanced by addition of alkylamine as an amphiphilic extractant. This alkylamine/octanol system exhibited amine basicity, and thus the pH of solution was controlled by equilibration with buffer. Further, enthalpy changes of the transfers of ATP and ADP from water to the alkylamine/octanol were estimated from van't Hoff analysis, and these enthalpy changes depended on ionization enthalpy of buffer. This result suggests that the transfers are accompanied with protonation of phosphoric ions and deprotonation of alkylamine. Finally, the partition coefficients of ATP, ADP, AMP, and Pi were estimated under the pH-controlled condition at 25 °C. The partition coefficients depended on the pH of aqueous phase and the net charge of phosphoric compounds. Therefore, the transfer is likely to be determined by electrostatic interaction between phosphoric ion and amine. The solvent system with a nucleotide-uptake capacity may partly mimic the function of ATP-binding proteins.

    Scopus

口頭発表・ポスター発表等 【 表示 / 非表示

  • アクチンの重合と脱重合の熱測定

    呉尚諭,小松英幸

    第58回日本生物物理学会年会  (オンライン)  2020年09月  -  2020年09月    日本生物物理学会

  • 熱量および蛍光滴定により推定されたタウ–DNA結合熱

    松田貫,鹿嶋純太,小松英幸

    第58回日本生物物理学会年会  (オンライン)  2020年09月  -  2020年09月    日本生物物理学会

  • タウー微小管とタウーヘパリン相互作用の等温滴定熱測定の比較

    鹿嶋純太,岡本里桜,小松英幸

    第58回日本生物物理学会年会  (オンライン)  2020年09月  -  2020年09月    日本生物物理学会

  • ATPータンパク質間相互作用を模倣した溶媒モデル

    小松英幸

    日本生体エネルギー研究会 第45回討論会  (九州工業大学 戸畑キャンパス)  2019年12月  -  2019年12月    日本生体エネルギー研究会

  • タウ-微小管相互作用の等温滴定熱測定

    Junta Kashima, Hiroshi Sakamoto, Junichi Taira, Hideyuki Komatsu

    第57回日本生物物理学会年会  (宮崎シーガイアコンベンションセンター)  2019年09月  -  2019年09月    日本生物物理学会

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科研費獲得実績 【 表示 / 非表示

  • 生体内遊離ヘムの濃度測定と動態解析

    基盤研究(C)

    研究期間:  2015年04月  -  2018年03月

    研究課題番号:  15K01825

  • ヘムオキシゲナーゼの触媒機構と蛋白質間相互作用ネットワークの解明

    基盤研究(C)

    研究期間:  2012年04月  -  2015年03月

    研究課題番号:  24510301

  • 有機溶媒相でのATP加水分解反応の速度論的及び熱力学的研究

    新学術領域研究

    研究期間:  2011年04月  -  2013年03月

    研究課題番号:  23118712

  • ATP加水分解自由エネルギーの分割

    新学術領域研究

    研究期間:  2009年04月  -  2011年03月

    研究課題番号:  21118517

  • リピート構造をもつ酸素が糖鎖上を解離せずに移動するメカニズム

    奨励研究(A)→若手研究(B)

    研究期間:  2001年04月  -  2003年03月

    研究課題番号:  13780537

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担当授業科目 【 表示 / 非表示

  • 2020年度  生命物理化学特論

  • 2020年度  生命化学情報工学実験Ⅱ

  • 2019年度  生命物理化学特論

  • 2019年度  情報工学概論

  • 2014年度  化学熱力学・演習

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