Interaction between Rheb and NR1 (6BT0)
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Rheb is a monomeric protein with a molecular weight of ~21kDa and is crucial in the activation of the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 is a master regulator of ceullar growth and metabolism and also plays an important role in protein synthesis. There have been several chronic diseases that have been associated with aberrant mTORC1 and so it is an important area that needs ongoing research. NR1 is an inhibitor of Rheb that selectively blocks mTORC1 signalling by occupying the hydrophobic pocket of the switch II domain of Rheb. The inhibition of Rheb by NR1 allows it to act as a therapeutic target in mTORC1 signalling. Reference: Nat Commun. 2018 Feb 7;9(1):548. A small molecule inhibitor of Rheb selectively targets mTORC1 signaling.
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