Communication
ChemComm
to be 0.29 mM and 1.17 mM (Fig. S7B, ESI‡) respectively, therefore, 10 A. A. Hamers, R. N. Hanna, H. Nowyhed, C. C. Hedrick and C. J.
de Vries, Curr. Opin. Lipidol., 2013, 24, 381–385.
2
K is equal to 0.23 mM according to eqn (2). This derived result
showed that the reversible covalent bond formation increased the
binding affinity and rendered celastrol more potent.
In conclusion, using diverse approaches, we have demon-
strated and confirmed that celastrol binds to the target protein
Nur77 via a Michael addition reaction at C551 in Nur77.
Importantly, the formation of this covalent bond is reversible
and requires specific noncovalent interactions with Nur77 to
1
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9 I. M. Serafimova, M. A. Pufall, S. Krishnan, K. Duda, M. S. Cohen,
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Conflicts of interest
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1 M. M. Mysinger, D. R. Weiss, J. J. Ziarek, S. Gravel, A. K. Doak,
J. Karpiak, N. Heveker, B. K. Shoichet and B. F. Volkman, Proc. Natl.
Acad. Sci. U. S. A., 2012, 109, 5517–5522.
There are no conflicts to declare.
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2 M. P. Jacobson, D. L. Pincus, C. S. Rapp, T. J. F. Day, T. B. Honig,
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2874 | Chem. Commun., 2018, 54, 12871--12874
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