Structure of HIV-1 Protease Determined by Neutron Crystallography

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  • HIV-1プロテアーゼの中性子結晶構造解析
  • サイエンス記事 HIV-1プロテアーゼの中性子結晶構造解析
  • サイエンス キジ HIV 1 プロテアーゼ ノ チュウセイシ ケッショウ コウゾウ カイセキ

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Abstract

<p>HIV-1 protease is an aspartic protease, and plays an essential role in replication of HIV. To develop HIV-1 protease inhibitors through structure-based drug design, it is necessary to understand the catalytic mechanism and inhibitor recognition of HIV-1 protease. We have determined the crystal structure of HIV-1 protease in complex with KNI-272 to 1.9 Å resolution by neutron crystallography in combination with 1.4 Å resolution X-ray diffraction data. The results show that the carbonyl group of hydroxymethylcarbonyl (HMC) in KNI-272 forms a hydrogen bonding interaction with protonated Asp 25 and the hydrogen atom from the hydroxyl group of HMC forms a hydrogen bonding interaction with the deprotonated Asp125. This is the first neutron report for HIV-1/inhibitor complex and shows directly the locations of key hydrogen atoms in catalysis and in the binding of a transition-state analog. The results confirm key aspects of the presumed catalytic mechanism of HIV-1 protease and will aid in the further development of protease inhibitors.</p>

Journal

  • hamon

    hamon 19 (4), 214-217, 2009

    The Japanese Society for Neutron Science

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