@article{9afa11bc16354e739de654780b36f3ab,
title = "Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca2+ pumps with a unique mode of binding",
abstract = "Biselyngbyasides (BLSs), macrolides from a marine cyanobacterium, are cytotoxic natural products whose target molecule is unknown. Here we report that BLSs are high affinity (Ki ∼ 10 nM) inhibitors of Ca2+-pumps with a unique binding mode. The crystal structures of the Ca2+-pump in complex with BLSs at 3.2-3.5 {\AA}-resolution show that BLSs bind to the pump near the cytoplasmic surface of the transmembrane region. The crystal structures and activity measurement of BLS analogs allow us to identify the structural features that confer high potency to BLSs as inhibitors of the pump.",
keywords = "Ca2+-ATPase, Crystal structure, High affinity, Inhibitor, Ion pump, Macrolide",
author = "Maho Morita and Haruo Ogawa and Osamu Ohno and Takao Yamori and Kiyotake Suenaga and Chikashi Toyoshima",
note = "Funding Information: We thank K. Hasegawa and H. Okumura of the Japan Synchrotron Radiation Research Institute (JASRI) for data collection at BL41XU of SPring-8 and J. Tsueda for preparing purified enzyme. We are grateful to D.B. McIntosh for help in improving the manuscript. This work was supported by a Specially Promoted Project Grant (23000014 to C.T.) and Grants-in-Aid (241310160 to K.S. and 13J00542 to M.M.) from Ministry of Education, Culture, Sports, Science, and Technology of Japan. Publisher Copyright: {\textcopyright} 2015 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. {\textcopyright} 2015 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.",
year = "2015",
month = may,
day = "26",
doi = "10.1016/j.febslet.2015.04.056",
language = "English",
volume = "589",
pages = "1406--1411",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "13",
}
