Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca2+ pumps with a unique mode of binding

Maho Morita; Haruo Ogawa; Osamu Ohno; Takao Yamori; Kiyotake Suenaga; Chikashi Toyoshima

doi:10.1016/j.febslet.2015.04.056

Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca²⁺ pumps with a unique mode of binding

Maho Morita, Haruo Ogawa, Osamu Ohno, Takao Yamori, Kiyotake Suenaga, Chikashi Toyoshima

Department of Chemistry

Research output: Contribution to journal › Article

13 Citations (Scopus)

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 (K_i ∼ 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	https://doi.org/10.1016/j.febslet.2015.04.056
Publication status	Published - 2015 May 26

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Keywords

Ca2+-ATPase
Crystal structure
High affinity
Inhibitor
Ion pump
Macrolide

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

Cite this

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

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AU - Suenaga, Kiyotake

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Access to Document

10.1016/j.febslet.2015.04.056