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Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca 2+ pumps with a unique mode of binding
Author(s) -
Morita Maho,
Ogawa Haruo,
Ohno Osamu,
Yamori Takao,
Suenaga Kiyotake,
Toyoshima Chikashi
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.04.056
Subject(s) - chemistry , cytotoxic t cell , transmembrane protein , stereochemistry , biochemistry , in vitro , receptor
Biselyngbyasides (BLSs), macrolides from a marine cyanobacterium, are cytotoxic natural products whose target molecule is unknown. Here we report that BLSs are high affinity ( K i ∼ 10 nM) inhibitors of Ca 2+ ‐pumps with a unique binding mode. The crystal structures of the Ca 2+ ‐pump in complex with BLSs at 3.2–3.5 Å‐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.