• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Basic study of drug development for anti-influenza virus based on structural analysis of sialidase

Research Project

Project/Area Number 16570104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionHigh Energy Accelerator Research Organization (KEK)

Principal Investigator

KATO Ryuichi  High Energy Accelerator Research Organization (KEK), Institute of Materials Structure Science, Associate Professor, 物質構造科学研究所, 助教授 (50240833)

Co-Investigator(Kenkyū-buntansha) WAKATSUKI Soichi  High Energy Accelerator Research Organization (KEK), Institute of Materials Structure Science, Professor, 物質構造科学研究所, 教授 (00332114)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordssialidase / neuraminidase / Neu2 / X-ray crystallography / three-dimensional structure / inhibitor / model building / complex / 酵素活性
Research Abstract

Neuraminidases, or sialidases, are glycohydrolytic enzymes broadly present among species. They are found in viruses, bacteria and mammals, where they catalyze the removal of sialic acid on the non-reducing termini of complex carbohydrates, and act in infection processes, signal transduction, intercellular interactions, glycoconjugate degradation etc. The infectivity of some viruses such as influenza virus has been illustrated to be biologically dependent on sialidase's function. For instance, the influenza virus neuraminidase (NA) hydrolyzes the sialic acid from a receptor protein located at the surface of the host cell and recognized by newly generated virus particles. In such a way, NA helps for the propagation of newly formed virions. Therefore, the inactivation of NA results in stopping the propagation of the virus. From this point of view, NA is the target of drug designs for clinical treatment of the infection. Within species, sialidases diverge in their amino acid sequences, but assume a similar folding by means of a six bladed beta-propeller, and share almost identical active site architecture. Consequently, drugs targeted to one virus strain's NA expectedly acts on other strains as well. We solved the X-ray crystal structure of the human sialidase Neu2, both alone and in complex with a sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid (DANA). Furthermore, we also determined the complex structures of human sialidase Neu2 with some NA inhibitors such as Zanamivir or Peramivir. Comparing the structures with that of influenza virus NA, more specific drug developments without side effect could be discussed.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (5 results)

All 2006 2005

All Journal Article (5 results)

  • [Journal Article] Structural basis for the inhibition of human cytosolic sialidase Neu2 by influenza virus drugs2006

    • Author(s)
      Kato R
    • Journal Title

      Trends in Glycoscience and Glycotechnology 18

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamice nature of substrate recognition2005

    • Author(s)
      Chavas LM
    • Journal Title

      J Biol Chem. 280

      Pages: 469-475

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Crystal structure of the human sialidase Neu22005

    • Author(s)
      Chavas LM
    • Journal Title

      Photon Factory Activity Report 22

      Pages: 44-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition2005

    • Author(s)
      Chavas LM
    • Journal Title

      J Biol Chem. 280

      Pages: 469-475

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition.2005

    • Author(s)
      Chavas LM, Tringali C, Fusi P, Venerando B, Tettamanti G, Kato R, Monti E. Wakatsuki S.
    • Journal Title

      J Biol Chem. 280

      Pages: 469-475

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi