About Us

Membrane proteins, including G protein-coupled receptors (GPCRs), transporters, ion channels, and integral membrane enzymes are involved in a large variety of pivotal biological functions and currently the most important class of therapeutic targets. Despite substantial interest in these targets, structure-based drug design (SBDD) has been challenging due to a paucity of high-resolution structural information. This is reflected in the difficulties encountered with the production, stability, and crystallization of membrane proteins. To overcome the bottlenecks, our laboratory has developed a state-of-the-art technical platform for membrane protein crystallography and has been studying structures of “druggable” membrane protein targets. The crystal structures will open up excellent opportunities in structure-based ligand discovery and/or SBDD. Research is being conducted in cooperation with the Membrane Protein Laboratory (MPL), a joint venture between the British synchrotron radiation facility Diamond Light Source and Imperial College London, as well as an X-ray free electron laser facility, SACLA, in Japan. Our laboratory is ideal for postdoctoral fellows and graduate students who aspire to build up an international career.

X-ray crystallography of human G protein-coupled receptors (GPCRs).

In silico docking simulations of second-generation selective H1R antagonists with the H1R ligand-binding pocket.

  • (a) A model of H1R complexed with levocetirizine.
  • (b) A model of H1R complexed with fexofenadine.
 

Recent Selected Publications

New!
Arakawa T, Kobayashi-Yurugi T, Alguel Y, Iwanari H, Hatae H, Iwata M, Abe Y, Hino T, Ikeda-Suno C, Kuma H, Kang D, Murata T, Hamakubo T, Cameron AD, Kobayashi T, Hamasaki N, Iwata S. (2015)
Crystal structure of the anion exchanger domain of human erythrocyte band 3.
Science 350(6261): 680-684.
DOI:10.1126/science.aaa4335. PubMed ID: 26542571
Related PDB Entries: 4YZF
Nomura, N., Verdon, G,. Kang, HJ., Shimamura, T., Nomura, Y., Sonoda, Y., Hussien, SA., Qureshi, AA., Coincon, M., Sato, Y., Abe, H., Nakada-Nakura, Y., Hino, T., Arakawa, T., Kusano-Arai, O., Iwanari, H., Murata, T., Kobayashi, T., Hamakubo, T., Kasahara, M., Iwata, S. and Drew, D. (2015)
Nature 526; 397-401(2015)
DOI:10.1038/nature14909. PubMed ID: 26416735
Related PDB Entries: 4YB9,4YBQ
Manolaridis, I., Kulkarni, K., Dodd, RD., Ogasawara, S., Zhang, Z., Bineva, G., O’Reilly, N., Hanrahan, SJ., Thompson, AJ., Cronin, N., S, Iwata., Barford, D.(2013)
Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1.
Nature. 504(7479):301-305.
DOI:10.1038/nature12754 PubMed ID: 2429179
Related PDB Entries:4CAD,
Hino,T., Arakawa,T., Iwanari,H., Yurugi-kobayashi,T., Ikeda-Suno,C., Nakada-Nakura,Y., Kusano-Arai, O., Weyand,S., Shimamura,T., Nomura,N., Cameron,A.D., Kobayashi,T., Hamakubo,T., Iwata,S. Murata,T. (2012)
G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody.
Nature 482: 237-240.
DOI:10.1038/nature10750 PubMed ID:22286059
Related PDB Entries:3VGA, 3VG9
Haga K, Kruse AC, Asada H, Yurugi-Kobayashi T, Shiroishi M, Zhang C, Weis WI, Okada T, Kobilka BK, Haga T, Kobayashi T. (2012)
Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist.
Nature 482:547-551.
DOI:10.1038/nature10753 PubMed ID: 22278061
Related PDB Entries:3UON,
Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S. (2011)
Structure of the human histamine H1 receptor complex with doxepin.
Nature 475: 65-72.
DOI:10.1038/nature10236 PubMed ID:21697825
Related PDB Entries:3RZE
Hu NJ, Iwata S, Cameron AD, Drew D. (2011)
Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.
Nature 478: 408-411.
DOI:10.1038/nature10450 PubMed ID:21976025
Related PDB Entries:3ZUY, 3ZUX
Hino, T., Matsumoto, Y., Nagano, S., Sugimoto, H., Fukumori, Y., Murata, T., Iwata, S., Shiro, Y. (2010)
Structural Basis of Biological N2O Generation by Bacterial Nitric Oxide Reductase.
Science 330: 1666-1670.
DOI:10.1126/science.1195591 PubMed ID:21109633
Related PDB Entries:3O0R
Shimamura, T., Weyand, S., Beckstein, O., Rutherford, N.G., Hadden, J.M., David Sharples, D., Sansom, M.S.P., Iwata, S., Henderson P.J.F. & Cameron, A.D. (2010)
Molecular Basis of Alternating Access Membrane Transport by the Sodium-Hydantoin Transporter, Mhp1.
Science 328: 470-473.
DOI:10.1126/science.1186303 PubMed ID:20413494
Related PDB Entries:2X79