Synthesis of a stable form of tertiapin:: A high-affinity inhibitor for inward-rectifier K+ channels
Synthesis of a stable form of tertiapin:: A high-affinity inhibitor for inward-rectifier K+ channels
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DOI：
10.1021/bi991205r
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发表时间：
1999-10-26
期刊：
影响因子：
2.9
通讯作者：
Lu, Z
中科院分区：
文献类型：
--
作者：
Jin, WL;Lu, Z
Tertiapin（TPN）：一种来源于蜜蜂毒液的小蛋白，以纳摩尔亲和力抑制GIRK 1/4和ROMK 1通道。TPN中的蛋氨酸残基13与通道中的残基F148相互作用，位于ROMK 1孔狭窄区域的外部。TPN中的甲硫氨酸残基可被空气氧化，这显著阻碍了TPN与通道的结合。为了克服由于M13的氧化导致的TPN亲和力的降低，我们用14个不同的残基替换了TPN中的M13。在这14种衍生物中，只有M13被谷氨酰胺取代的衍生物TPNQ与通道结合的Ki值与天然TPN非常相似。由于TPNQ是稳定的，并且功能上与天然TPN相似，因此它将是研究内向整流钾通道非常有用的分子探针。
Tertiapin (TPN): a small protein derived from honey bee venom, inhibits the GIRK1/4 and ROMK1 channels with nanomolar affinities. Methionine residue 13 in TPN interacts with residue F148 in the channel, located just outside of the narrow region of the ROMK1 pore. The methionine residue in TPN can be oxidized by air, which significantly hinders TPN binding to the channels. To overcome the reduction in TPN affinity due to oxidation of M13, we replaced M13 in TPN with fourteen different residues. Out of the fourteen derivatives, only the one in which M13 was replaced by glutamine, TPNQ, binds to the channel with a K-i value very similar to that of native TPN, Since TPNQ is stable and functionally resembles native TPN, it will be a very useful molecular probe for studying the inward-rectifier K+ channels.