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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1406-1411 |
| Number of pages | 6 |
| Journal | FEBS Letters |
| Volume | 589 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 2015 May 26 |
Keywords
- Ca2+-ATPase
- Crystal structure
- High affinity
- Inhibitor
- Ion pump
- Macrolide
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
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Morita, M., Ogawa, H., Ohno, O., Yamori, T., Suenaga, K., & Toyoshima, C. (2015). Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca2+ pumps with a unique mode of binding. FEBS Letters, 589(13), 1406-1411. https://doi.org/10.1016/j.febslet.2015.04.056