8.C.4. The Macrolide Bisolyngbyaside Inhibitors of Ca²⁺-ATPases (BLS) Family

Biselyngbyasides (BLSs), macrolides from marine cyanobacteria, are cytotoxic natural products that are high affinity (Ki approximately 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 A-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 reveal the structural features that confer high potency to BLSs as inhibitors of the pump (Morita et al. 2015).

References:

Morita, M., H. Ogawa, O. Ohno, T. Yamori, K. Suenaga, and C. Toyoshima. (2015). Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca²⁺ pumps with a unique mode of binding. FEBS Lett. 589: 1406-1411.