Dynamic Structural Modeling Revealed That Nilotinib Inhibits Smoothened Signaling
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چکیده
منابع مشابه
Pyrvinium attenuates Hedgehog signaling downstream of smoothened.
The Hedgehog (HH) signaling pathway represents an important class of emerging developmental signaling pathways that play critical roles in the genesis of a large number of human cancers. The pharmaceutical industry is currently focused on developing small molecules targeting Smoothened (Smo), a key signaling effector of the HH pathway that regulates the levels and activity of the Gli family of ...
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An intracellular conformational switch in the serpentine transmembrane protein Smoothened appears to underlie Hedgehog pathway activation. The switch is gated by electrostatic interactions that are regulated by multiple phosphorylations, potentially endowing a dose-dependent response.
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Protein kinase A (PKA) is a prototype of multidomain signaling proteins functioning as allosteric conformational switches. Allosteric transitions have been the subject of extensive structural and dynamic investigations focusing mainly on folded domains. However, the current understanding of the allosteric role of partially unstructured linkers flanking globular domains is limited. Here, we show...
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ژورنال
عنوان ژورنال: Neurosurgery
سال: 2019
ISSN: 0148-396X,1524-4040
DOI: 10.1093/neuros/nyz310_806