Success in Crystallization of Protein (BAT) in the International Space Station and its X-ray Crystallographic Analysis back on earth!

Professor Masanori Sugiyama of the Graduate School of Biomedical Sciences who used land and the International Space Station (ISS) for his research had his results posted in the American Society for Biochemistry and Molecular Biology academic journal, the Journal of Biological Chemistry (JBC), on January 8th of this year (electronically presented in November of last year).

Professor Sugiyama discovered in 1994 an enzyme (bleomycin N-Acetyltransferase: BAT) that can inactivate an anti-cancer agent bleomycin (Bm) through a process of acetylation.

Bm, which is bound with iron (Fe), activates oxygen. Since the activated oxygen causes DNA cleavage, the proliferation of cancer cells is inhibited. Although the inhibitory effects of Bm on cancer cells are high, the drug occasionally causes pneumonitis and pulmonary fibrosis as side effects.
Bm acetylated by BAT does not exhibit anti-cancer activity, and it does not induce in vitro DNA degradation.

Professor Sugiyama's group believed if they could determine the three-dimensional structure of BAT, they could develop a new Bm derivative containing the high cleaving activity but lose its side effects, which is why they engaged in their research of the X-ray crystal structure analysis of BAT.

However, above ground, it was difficult to obtain a suitable crystal of BAT necessary for high quality crystallographic analysis. After having stalled the crystallization, Professor Sugiyama received news that JAXA (Japan Aerospace Exploration Agency) had made a public advertisement of the possibility to conduct an experimental project aboard the ISS, to which he responded.
Russia’s spacecraft was used to transport the BAT protein solution to the ISS, which took another 3~4 months in micro-gravity field to complete the crystallization. After the crystal was retrieved back to earth, the diffraction intensities of the crystals were obtained using synchrotron radiation at Synchrotron Radiation Facility SPring-8 (Sayo-cho, Hyogo Prefecture). The three-dimensional structure of BAT was then determined splendidly.

In addition to the crystallization of BAT in its uncomplexed state, BAT complexed with acetyl-CoA (a substrate of BAT), and the Bm・CoA・BAT complex were crystallized on　earth; these X-ray crystal structures were successfully determined.

With structural information of protein, we can use the understanding correlation between its function and structure to make progress in creating new drug design and novel protein for which we have high expectations.

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