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HHHe

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应助: 0 (幼儿园)
金币: 1599.4
散金: 20
帖子: 48
在线: 6.8小时
虫号: 3943183
注册: 2015-06-27
专业: 分析仪器与试剂

[求助] Small molecule modulation of Smoothened activity，Smoothened这里是受体的意思吗？

Smoothened (Smo), a distant relative of G protein-coupled receptors, mediates Hedgehog (Hh) signaling during embryonic development and can initiate or transmit ligand-independent pathwayactivation in tumorigenesis. Although the cellular mechanisms that
regulate Smo function remain unclear, the direct inhibition of Smo by cyclopamine, a plant-derived steroidal alkaloid, suggests that
endogenous small molecules may be involved. Here we demonstrate that SAG, a chlorobenzothiophene-containing Hh pathway
agonist, binds to the Smo heptahelical bundle in a manner that
antagonizes cyclopamine action. In addition, we have identified
four small molecules that directly inhibit Smo activity but are
structurally distinct from cyclopamine. Functional and biochemical
studies of these compounds provide evidence for the small molecule modulation of Smo through multiple mechanisms and yield
insights into the physiological regulation of Smo activity. The
mechanistic differences between the Smo antagonists may be
useful in the therapeutic manipulation of Hh signaling.

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