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2015 Fiscal Year Research-status Report

Thermodynamic basis of life: protein-carbohydrate interaction

Research Project

Project/Area Number 15K06962
Research InstitutionThe University of Tokyo

Principal Investigator

CAAVEIRO Jose  東京大学, 工学(系)研究科(研究院), 研究員 (00536732)

Project Period (FY) 2015-04-01 – 2018-03-31
KeywordsGlycan / Sugar / Antibody / Enzyme / Pore forming protein / X-ray Crystallography / Thermodynamics / Kinetics
Outline of Annual Research Achievements

1. Data collection and analysis of proteins GalM, FraC, and other systems in which sugars play an important role such as antibodies. These data were necessary to make progress in the project according to the plan described last year. Specifically the crystallographic, enzymatic, mutagenesis and biophysical analysis work have progressed adequately and we are ready to start the preparation of more manuscripts describing these results.

2. Presentation of data at two international conferences (Pacifichem2015) and a Gordon Conference. These two meetings were ideal to publicize our research and to get feedback from senior researchers in the field. I made contacts with some of these researchers with the goal of establishing international collaborations.

3. Publication of three manuscripts in highly regarded international journals, highlighting our work and facilitating the graduation of a Ph.D. student (also winner of the 6th Ikushi Prize 【育志賞】).

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

1. Data acquisition and analysis is progressing well, specially for the pore forming protein FraC. The goals for the fiscal year 2015 were achieved.
2. Data was published in scientific journals as described elsewhere, and presented at international conferences.

Strategy for Future Research Activity

1. GalM. In particular I will analyze more structural, thermodynamic and functional data. The use of sugar containing an atom of sulfur (thio-sugars) will enlighten the selectivity and prowess of the enzyme. These results will be summarized in two manuscripts to be submitted to international per-reviewed journals and presented at an international conference.
2. Characterize the sugar binding and function of FraC. We have already identified some sugars binding to a shared binding site, and our goal is to determine the exact position of that binding site in the architecture of the protein, and the importance for its function. I would like to employ bioinformatic techniques to understand the generality of these findings. These results will also be summarized in one or two manuscripts to be submitted to international per-reviewed journals and presented at international conferences.

  • Research Products

    (7 results)

All 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Structural Analysis of Fc/FcγR Complexes: A Blueprint for Antibody Design.2015

    • Author(s)
      Caaveiro, J.M.M., Kiyoshi, M. and Tsumoto, K.
    • Journal Title

      Immunological Reviews

      Volume: 268 Pages: 201-221

    • DOI

      10.1111/imr.12365

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structural and thermodynamics basis of epitope binding to neutralizing and non-neutralizing forms of the anti-HIV-1 4E10 antibody2015

    • Author(s)
      Rujas, E., Gulzar, N., Morante, K., Tsumoto, K., Scott, J.K., Nieva, J.L. and Caaveiro, J.M.M.
    • Journal Title

      Journal of Virology

      Volume: 89 Pages: 11975-11991

    • DOI

      10.1128/JVI.01793-15

    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Bidirectional transformation of a protein between its Native Water-Soluble and Transmembrane Conformations.2015

    • Author(s)
      Tanaka, K., Caaveiro, J.M.M., and Tsumoto, K.
    • Journal Title

      Biochemistry

      Volume: 54 Pages: 6863-6866

    • DOI

      10.1021/acs.biochem.5b01112

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Principles of Biomolecular Recognition of IgG-Fc by its receptors2016

    • Author(s)
      Caaveiro, J.M.M., Kiyoshi, M. and Tsumoto, K.
    • Organizer
      Gordon Conference (Antibody Biology and Engineering)
    • Place of Presentation
      Galveston, TX, USA
    • Year and Date
      2016-03-20 – 2016-03-25
  • [Presentation] Structural and mechanistic basis of capsular polysaccharide-synthesizing enzymes CapE/F, and the route to discovery novel inhibitors with antibacterial properties.2015

    • Author(s)
      Caaveiro J.M.M., Miyafusa, T., Chigira, T., Nakano, K., Nagatoishi, S. and Tsumoto, K.
    • Organizer
      7th International Chemical Congress of Pacific Basin Societies PacificChem
    • Place of Presentation
      Honolulu, HI, USA
    • Year and Date
      2015-12-18 – 2015-12-18
    • Int'l Joint Research
  • [Presentation] Molecular basis of heme transfer between NEAT transporters in Staphylococcus aureus2015

    • Author(s)
      Caaveiro, J.M.M., Morante, K., Vu, N., Moriwaki, Y., and Tsumoto, K.
    • Organizer
      7th International Chemical Congress of Pacific Basin Societies PacificChem
    • Place of Presentation
      Honolulu, HI, USA
    • Year and Date
      2015-12-17 – 2015-12-17
    • Int'l Joint Research
  • [Presentation] Use of thermodynamic tools in the early stages of fragment-based drug discovery2015

    • Author(s)
      Caaveiro J.M.M., Kobe, A., Mitani, T. and Tsumoto, K
    • Organizer
      7th International Chemical Congress of Pacific Basin Societies PacificChem
    • Place of Presentation
      Honolulu, HI, USA
    • Year and Date
      2015-12-16 – 2015-12-16
    • Int'l Joint Research

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Published: 2017-01-06  

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