TY - JOUR
T1 - A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A
AU - Ottmann, C.
AU - Weyand, M.
AU - Sassa, T.
AU - Inoue, T.
AU - Kato, N.
AU - Wittinghofer, A.
AU - Oecking, C.
PY - 2009
Y1 - 2009
N2 - 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,
AB - 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,
U2 - 10.1016/j.jmb.2009.01.005
DO - 10.1016/j.jmb.2009.01.005
M3 - Article
SN - 0022-2836
VL - 386
SP - 913
EP - 919
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 4
ER -
