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Chuck Reynolds
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What does Resveratrol induce.? P-9, P-2

Published on 6/19/2019
For additional information  Click Here

Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition P-9


Resveratrol was initially identified as a SIRT1 activator because of its structural similarity to quercetin. Considering that quercetin is known to inhibit a broad spectrum of kinases in an ATP-competitive manner and that resveratrol also inhibits several kinases, increased the possibility of ATP competitive mode of action of resveratrol in mTOR inhibition. To test the possibility that resveratrol directly binds in the ATP-binding site of mTOR, we carried out docking simulations between mTOR and resveratrol. Detailed binding mode analysis of resveratrol implied that its binding in the ATP-binding site of mTOR could be facilitated by the establishment of multiple hydrogen bonds with the backbone amide groups in the hinge region and the side chains of E2190 and D2195.

Simultaneously, hydrophobic interactions with the nonpolar residues in the ATP-binding pocket were also found to be a significant binding force that stabilizes the mTOR-resveratrol complex. These computational results may serve as persuasive evidence for competitive inhibition of mTOR by resveratrol. An analysis of mTOR activity using a putative resveratrol binding-defective mutant verified this result by showing that resveratrol suppressed WT mTOR but not D2195A mTOR). The Asp 2195 residue is also involved in mTOR-PP242 binding. However, PP242 inhibited the D2195A mutant, though its potency was reduced compared to WT mTOR. This result indicates that Asp 2195 is a key residue for mTOR-resveratrol binding.

Article Produced By

Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea

(All these Articles can be read with this URL: )

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Chuck Reynolds

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