Studies on molecular recognition mechanisms of biomolecules and their application

在细胞表面，存在许多受体蛋白，特定的生物分子被这些受体蛋白识别。这些机理可以从化学的角度进行分析。为了使生物靶化系统，本文对这些生物分子的识别机制进行了研究。Imanaka博士研究了酶的分子识别机制，并发现了许多具有不寻常分子识别（底物和辅因子特异性）的酶。对一种超嗜热古细菌柯达卡拉热球菌KOD 1进行了研究。对各种酶进行了详细的酶分析和结构分析。大竹博士研究了铜绿假单胞菌趋化的分子机制。P. aeruginosa被20种常见的l -氨基酸、有机酸、芳香族化合物、O_2和无机磷酸盐（P_I）吸引。P. aeruginosa对硫氰酸酯、异硫氰酸酯和挥发性氯代脂肪化合物表现出负的趋化反应。Sode博士研究了一种基于β-螺旋桨蛋白（BPP）分子结构构建蛋白质的新策略。通过构建多嵌合酶，证实了PQQGDH在BPP中引入的功能区的累积效应。研究还证实了具有相似支架的两种不同BPP之间的w基序交换，显示了基于BPP支架的新型蛋白结构的未来发展。Takagi博士研究了一种植物特异性肽，植物螯合素（phytochelatin， PC）解毒Cd^<2+>引起的细胞凋亡；（γ - glys）n-Gly)以及抗氧化剂（谷胱甘肽（GSH）和n-乙酰半胱氨酸（NAC））。抗氧化剂可以解毒Cd^<2+>引起的氧化应激。PC的解毒作用强于抗氧化剂，且与Bcl-2具有协同作用。通过将拟南芥的PC合成酶基因转移到jurkat细胞中，在哺乳动物细胞中产生了植物特异性的PC，转化后的jurkat细胞产生了PC，并表现出对Cd^<2+>的抗性。少

In cell surface, many recepter proteins are presented and the specific biomolecules are recognized by these recepter proteins. These mechanisms can be analyzed from chemical view points. To systemize the biotergeting, the recognition mechanism of these biomolecules were investigated. Dr. Imanaka studied mechanisms of molecular recognition for enzymes, and also discovered many enzymes with unusual molecular recognition (substrate and cofactor specificity). A hyperthermophilic archaeon, Thermococcus kodakaraensis KOD 1 was focused on. Detailed enzymatic analysis, along with structural analysis has been performed for various enzymes. Dr. Ohtake studied molecular mechanisms of chemotaxis in Pseudomonas aeruginosa. P. aeruginosa was attracted by 20 commonly occurring L-amino acids, organic acids, aromatic compounds, O_2, and inorganic phosphate (P_I). P. aeruginosa showed negative chemotactic responses toward thiocyanate and isothiocyanate esters, and volatile chlorinated aliphatic compound … More s. The methyl-accepting chemotaxis protein (MCP)-dependent pathway was analyzed in detail. Dr. Sode studied a novel strategy for the construction of proteins based on the molecular architecture of β-propeller protein (BPP). By multichimeric enzyme construction, the cumulative effect of functional regions of PQQGDH introduced in BPP was demonstrated. It was also demonstrated the W-motif exchange between two different BPP with similar scaffold, showing the future development of novel protein constructs based on BPP scaffolds. Dr. Takagi studied apoptosis caused by Cd^<2+> detoxification by a plant specific peptide, phytochelatin (Phytochelatin (PC) ; (gamma-Glu-Cys)n-Gly) as well as antioxidants (glutathione (GSH) and N-acetyl cysteine (NAC)). Antioxidants could detoxify Cd^<2+> toxicity that Cd^<2+> causes oxidative stress. Detoxification by PC was stronger than that by antioxidants and the effect seems to be synergistic with Bcl-2. Production of the plant specific PC in mammalian cells was attempted by transferring a gene for PC synthase from Arabidopsis dialiana to jurkat cell and transformed Jurkat cells produced PC and exhibited resistance to Cd^<2+>. Less