東京大学 · 생화학·유전·분자생물학
쿠헤이 츠모토 교수의 연구실은 항체의 구조-기능 관계와 항체 기반 치료제의 최적화를 핵심으로 삼고 있습니다. 고친수치(affinity) 항체의 설계 및 안정성 분석을 위해 구조 생물학, 생화학적 분석, 그리고 컴퓨터 기반의 가상 스크리닝 기법을 융합적으로 활용하고 있으며, 특히 항원-항체 상호작용의 분자 기반을 규명하는 데 초점을 맞추고 있습니다. 또한 병원성 박테리아의 철 흡수 메커니즘을 해독하는 데서도 생체 분자 간의 고해상도 상호작용을 연구하는 데 기여하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM) for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1). We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therap
To elucidate the heme acquisition system in pathogenic bacteria, we investigated the heme-binding properties of the third NEAT domain of IsdH (IsdH-NEAT3), a receptor for heme located on the surfaces of pathogenic bacterial cells, by using x-ray crystallography, isothermal titration calorimetry, examination of absorbance spectra, mutation analysis, size-exclusion chromatography, and analytical ultracentrifugation. We found the following: 1) IsdH-NEAT3 can bind with multiple heme molecules by two
To address how changes in the subclass of antibody molecules affect their thermodynamic stability, we prepared three types of four monoclonal antibody molecules (chimeric, humanized, and human) and analyzed their structural stability under thermal stress by using size-exclusion chromatography, differential scanning calorimetry (DSC), circular dichroism (CD), and differential scanning fluoroscopy (DSF) with SYPRO Orange as a dye probe. All four molecules showed the same trend in change of structu
It has been shown that Tyr residues are unusually localized in the regions of antibodies responsible for contact with antigens (Padlan, E. A. (1990) Proteins Struct. Funct. Genet. 7, 112-124). In order to clarify the role of these Tyr residues in antigen binding, the interaction between hen egg white lysozyme (HEL) and its monoclonal antibody HyHEL10, whose structure has been well studied in complex with its antigen, was investigated. Four Tyr residues in the VH chain (HTyr-33, HTyr-50, HTyr-53,
