Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca2+ pumps with a unique mode of binding
Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca2+ pumps with a unique mode of binding
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DOI：
10.1016/j.febslet.2015.04.056
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发表时间：
2015-06-04
期刊：
影响因子：
3.5
通讯作者：
Toyoshima, Chikashi
中科院分区：
文献类型：
--
作者：
Morita, Maho;Ogawa, Haruo;Toyoshima, Chikashi
双菱苦苷（Biselyngbyasides，BLSs）是一种来源于海洋蓝藻的大环内酯类化合物，具有细胞毒性，其作用靶分子尚不清楚。在这里，我们报告说，BLS是高亲和力（Ki类似于10 nM）的钙泵抑制剂，具有独特的结合模式。在3.2-3.5埃分辨率下与BLS复合的Ca 2+泵的晶体结构显示BLS在跨膜区的细胞质表面附近结合到泵。BLS类似物的晶体结构和活性测量使我们能够确定赋予BLS作为泵抑制剂的高效力的结构特征。(C)2015由Elsevier B. V.代表欧洲生物化学学会联合会出版。
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 similar to 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 angstrom-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. (C) 2015 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.