Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation |
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| Authors: | Dr. Haruhiko Ehara Marie Makino Dr. Koichiro Kodama Prof. Dr. Keiichi Konoki Dr. Takuhiro Ito Dr. Shun‐ichi Sekine Dr. Seketsu Fukuzawa Prof. Dr. Shigeyuki Yokoyama Prof. Dr. Kazuo Tachibana |
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| Affiliation: | 1. 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);2. RIKEN Systems and Structural Biology Center, 1‐7‐22, Suehiro‐cho, Tsurumi, Yokohama 230‐0045 (Japan);3. RIKEN Center for Life Science Technologies, 1‐7‐22, Suehiro‐cho, Tsurumi, Yokohama 230‐0045 (Japan);4. Department of Chemistry, Graduate School of Science, The University of Tokyo, 7‐3‐1, Hongo, Bunkyo‐ku, Tokyo 113‐0033 (Japan);5. Graduate School of Agricultural Science, Tohoku University, 1‐1 Tsutsumidori‐Amamiyamachi, Aoba‐ku, Sendai, Miyagi 981‐8555 (Japan);6. RIKEN Structural Biology Laboratory, 1‐7‐22, Suehiro‐cho, Tsurumi, Yokohama 230‐0045 (Japan) |
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| 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. |
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| Keywords: | marine cytotoxins okadaic acid protein structure sponges |
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