A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A

C. Ottmann, M. Weyand, T. Sassa, T. Inoue, N. Kato, A. Wittinghofer, C. Oecking

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Abstract

Cotylenin A, a fungal metabolite originally described as a cytokinin-like bioactive substance against plants shows differentiation-inducing and antitumor activity in certain human cancers. Here, we present the crystal structure of cotylenin A acting on a 14-3-3 regulatory protein complex. By comparison with the closely related, but non-anticancer agent fusicoccin A, a rationale for the activity of cotylenin A in human cancers is presented. This class of fusicoccane diterpenoids are possible general modulators of 14-3-3 protein-protein interactions. In this regard, specificities for individual 14-3-3/target protein complexes might be achieved by varying the substituent pattern of the diterpene ring system. As the different activities of fusicoccin A and cotylenin A in human cancers suggest, hydroxylation of C12 might be a sufficient determinant of structural specificity. (C) 2009 Elsevier Ltd. All rights reserved,
Original languageEnglish
Pages (from-to)913-919
JournalJournal of Molecular Biology
Volume386
Issue number4
DOIs
Publication statusPublished - 2009

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