Biometal Science Laboratory

Studies are concentrated on the structure and function of metalloproteins which are involved in biological redox reactions and in cellular signal transductions. Central problems are elucidation of the molecular mechanisms of the metalloenzymes on the basis of the molecular structures which are determined by the SPring-8 RIKEN beam line, artificial modeling/improvement of metalloprotein functions, and designing of new metalloproteins.

Research Subjects

• Structural and functional analyses of several metalloenzymes
• Structural and functional analyses of metalloproteins relating to cellular signal trasnduction
• Structural and functional studies of proteins related cellular metal dynamics
• Development and application of new methods to protein structural determination

Publications

1. Sugimoto, H., Oda, S., Otsuki, T., Hino, T., Yoshida, T., and Shiro, Y.:
   "Crystal Structure of Human Indoleamine 2,3-dioxygenase: Insighhts into the Catalytic Mechanism of O2 Incorporation by a Heme-containing Dioxygenase"
   Proc. Natl. Acad. Sci. USA, 103, 2611-2616 (2006)
2. Kumita, H., Matsuura, K., Hino, S., Hori, H., Fukumori, Y., Morishima, I., and Shiro, Y.:
   "NO Reduction by Nitric Oxide Reductase from Denitrifying Bacterium Pseudomonas aeruginosa: Characterization of Reaction Intermediates That Appear in the Single-Turnover Cycle"
   J. Biol. Chem., 279, 55247-55254 (2004).
3. Nakamura, H., Kumita, H., Imai, K., Iizuka, T., and Shiro, Y.:
   "ADP Reduces the Oxygen Affinity of a Semsory Histidine Kinase FixL: The Possibility of an Enhanced Reciprocating Kinase Reaction"
   Proc. Natl. Acad. Sci. USA, 101, 2742-2746 (2004).
4. Y. Matsumoto, T. Tosha, A. V. Pisliakov, T. Hino, H. Sugimoto, S. Nagano, Y. Sugita, Y. Shiro:
   "Crystal Structure of Quinol-Dependent Nitric Oxide Reductase from Geobacillus stearithermophilus"
   Nat. Strl. Mol. Biol. 19, 238-245 (2012)
5. S. Yamada, H. Sugimoto, M. Kobayashi, A. Ohno, H. Nakamura, Y. Shiro:
   "Structure of PAS-linked Histidine Kinase and the Response Regulator Complex"
   Structure 17, 1333-1344 (2009)
6. Y. Wang, H. Chen, M. Makino, Y. Shiro, S. Nagano, S. Asamizu, H. Onaka, S. Sason:
   "Theoretical and Experimental Studies of the Conversion of Chromopyrrolic Acid to an Antitumor Derivative by Cytochrome P450 StaP: The Biological Role of Water Molecules"
   J. Am. Chem. Soc. 131, 6748-6762 (2009)
7. O. Shoji, T. Fujishiro, H. Nakajima, M. Kim, S. Nagano, Y. Shiro, Y. Watanabe:
   "Hydrogen Peroxide Dependent Monooxygenations by Tricking the Substrate Recognition of Cytochrome P450BSβ"
   Angw. Chem. Int. Ed. 46, 3656-3659 (2007)
8. M. Makino, H. Sugimoto, Y. Shiro, S. Asamizu, H. Onaka, S. Nagano:
   "Crystal Structures and Catalytic Mechanism of Cytochrome P450 StaP That Produces The Indolocarbazole Skeleton"
   Proc. Natl. Acad. Sci. USA 104, 11591-11596 (2007)
9. H. Mizuno, T. K. Mal, M. Welchli, A. Kikuchi, T. Fukano, R. Ando, J. Jeyakanthan, J. Taka, Y. Shiro, M. Ikura, A. Miyawaki:
   "Light-dependent Regulation of Structural Flexibility in a Photochromic Fluorescent Protein"
   Proc. Natl. Acad. Sci. USA 105, 9927-9932 (2008)
10. T. Hino, Y. Matsumoto, S. Nagano, H. Sugimoto, Y. Fukumori, T. Murata, S. Iwata, Y. Shiro:
    "Structural Basis of Biological N2O Generation by Bacterial Nitric Oxide Reductase"
    Science 330, 1666-1670 (2010)