title: Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation.
abstract: Okadaic acid (OA) is a marine polyether cytotoxin that was first isolated from the marine sponge Halichondria okadai. OA is a potent inhibitor of protein serine/threonine phosphatases (PP) 1 and 2A, and the structural basis of phosphatase inhibition has been well investigated. However, the role and mechanism of OA retention in the marine sponge have remained elusive. We have solved the crystal structure of okadaic acid binding protein 2.1 (OABP2.1) isolated from H. okadai; it has strong affinity for OA and limited sequence homology to other proteins. The structure revealed that OABP2.1 consists of two α-helical domains, with the OA molecule deeply buried inside the protein. In addition, the global fold of OABP2.1 was unexpectedly similar to that of aequorin, a jellyfish photoprotein. The presence of structural homologues suggested that, by using similar protein scaffolds, marine invertebrates have developed diverse survival systems adapted to their living environments.
authors.affiliation: Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).|RIKEN Systems and Structural Biology Center, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan).|RIKEN Center for Life Science Technologies, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan).
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ehara
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Marie
authors.initials: M
authors.lastname: Makino
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kodama
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555 (Japan).
authors.forename: Keiichi
authors.initials: K
authors.lastname: Konoki
authors.affiliation: Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).|RIKEN Systems and Structural Biology Center, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan).|RIKEN Center for Life Science Technologies, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan).
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).|RIKEN Systems and Structural Biology Center, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan).|RIKEN Center for Life Science Technologies, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan).
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan). seketsuf@chem.s.u-tokyo.ac.jp.
authors.forename: Seketsu
authors.initials: S
authors.lastname: Fukuzawa
authors.affiliation: Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan). yokoyama@riken.jp.|RIKEN Systems and Structural Biology Center, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan). yokoyama@riken.jp.|RIKEN Structural Biology Laboratory, 1-7-22, Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan). yokoyama@riken.jp.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan). ktachi@chem.s.u-tokyo.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tachibana
mesh_terms: D000331:Aequorin / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D019319:Okadaic Acid / Q000378:metabolism*; D011161:Porifera / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D003603:Cytotoxins; D004791:Enzyme Inhibitors; D011506:Proteins; D019319:Okadaic Acid; D000331:Aequorin
keywords: marine cytotoxins; okadaic acid; protein structure; sponges