X-ray Structure Analysis of Human Oxidized Nucleotide Hydrolase MTH1 using Crystals Obtained under Microgravity

• NAKAMURA Teruya

  Priority Organization for Innovation and Excellence, Kumamoto University Graduate School of Pharmaceutical Sciences, Kumamoto University

• HIRATA Keisuke

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• FUJIMIYA Kana

  School of Pharmacy, Kumamoto University

• CHIRIFU Mami

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• ARIMORI Takao

  Institute for Protein Research, Osaka University

• TAMADA Taro

  Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology

• IKEMIZU Shinji

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• YAMAGATA Yuriko

  Graduate School of Pharmaceutical Sciences, Kumamoto University

Abstract

Human MTH1 hydrolyzes oxidized nucleoside triphosphates with broad substrate specificity and draws attention as a potential anticancer target. Recently, we determined the high resolution crystal structures of MTH1 and suggested that MTH1 recognizes different substrates via an exchange of the protonation state at Asp119 and Asp120. In order to validate this mechanism, it is essential to observe hydrogen atoms by ultra-high resolution X-ray crystallography and/or neutron crystallography using large high quality crystals. Here we carried out the crystallization of MTH1 in complex with a substrate, 8-oxo-dGTP, under microgravity in the Japanese Experiment Module ‘Kibo’. One of the crystals diffracted to 1.04-Å resolution, which is better than that we reported previously. We carried out bond length analysis of Asp119 and Asp120 using this updated data, which revealed the protonation state based on the bond lengths with higher accuracy and precision.

Journal

• International journal of microgravity science and application

  International journal of microgravity science and application 36 (1), 360103-, 2019

  The Japan Society of Microgravity Application

Keywords

• Substrate specificity
• Protonation, Aspartic acid

Details

• CRID: 1390283659831485312
• NII Article ID: 130007769928
• DOI: 10.15011//jasma.36.360103
• ISSN: 21889783
• Text Lang: en
• Data Source:
  • JaLC
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed