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

DOI:10.15011//jasma.36.360103
Int. J. Microgravity Sci. Appl. 2019p360103
Author
T. NAKAMURA, K. HIRATA, K. FUJIMIYA, M. CHIRIFU, T. ARIMORI, T. TAMADA, S. IKEMIZU and Y. YAMAGATA
Organization
Priority Organization for Innovation and Excellence, Kumamoto University, Graduate School of Pharmaceutical Sciences, Kumamoto University, School of Pharmacy, Kumamoto University, Institute for Protein Research, Osaka University, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology
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.
Keyword(s)
Substrate specificity, Protonation, Aspartic acid
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Received 16 October 2018, Accepted 8 January 2019, Published 31 January 2019.

© The Japan Society of Microgravity Applicaiton

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