3E6Y

Structure of 14-3-3 in complex with the differentiation-inducing agent Cotylenin A

Summary for 3E6Y

• Entry DOI: 10.2210/pdb3e6y/pdb
• Descriptor: 14-3-3-like protein C, H+-ATPase phosphopeptide QSYpTV, Cotylenin A, ... (5 entities in total)
• Functional Keywords: adapter protein, signaling protein
• Biological source: Nicotiana tabacum (American tobacco,tobacco); More
• Total number of polymer chains: 4
• Total formula weight: 61494.17

Authors

Ottmann, C.,Weyand, M.,Wittinghofer, A.,Oecking, C. (deposition date: 2008-08-17, release date: 2009-03-10, Last modification date: 2024-10-16)

Primary citation

Ottmann, C.,Weyand, M.,Sassa, T.,Inoue, T.,Kato, N.,Wittinghofer, A.,Oecking, C.
A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A
J.Mol.Biol., 386:913-919, 2009

PubMed Abstract: Cotylenin A, a fungal metabolite originally described as a cytokinin-like bioactive substance against plants shows differentiation-inducing and anti-tumor 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.

PubMed: 19244612

Experimental method

X-RAY DIFFRACTION (2.5 Å)