PDBsum entry 3e6y

Signaling protein

PDB id: 3e6y

Contents

Protein chains

234 a.a. *

Ligands

GLN-SER-TYR-TPO-VAL ×2

CW1 ×2

Metals

_CL

Waters ×100

* Residue conservation analysis

PDB id:

3e6y

Name:

Signaling protein

Title:

Structure of 14-3-3 in complex with the differentiation-inducing agent cotylenin a

Structure:

14-3-3-like protein c. Chain: a, b. Synonym: 14-3-3-like protein b. Engineered: yes. H+-atpase phosphopeptide qsyptv. Chain: c, d. Engineered: yes

Source:

Nicotiana tabacum. American tobacco,tobacco. Organism_taxid: 4097. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. It is found naturally in arabidopsis thaliana

Resolution:

2.50Å R-factor: 0.200 R-free: 0.285

Authors:

C.Ottmann,M.Weyand,A.Wittinghofer,C.Oecking

Key ref:

C.Ottmann et al. (2009). A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A. J Mol Biol, 386, 913-919. PubMed id: 19244612 DOI: 10.1016/j.jmb.2009.01.005

Date:

17-Aug-08 Release date: 10-Mar-09

Protein chains

P93343  (1433C_TOBAC) -  14-3-3-like protein C from Nicotiana tabacum

Seq: 260 a.a.

Struc: 234 a.a.

DOI no: 10.1016/j.jmb.2009.01.005

J Mol Biol 386:913-919 (2009)

PubMed id: 19244612

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.

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.

Selected figure(s)

Figure 1.
Fig. 1. Overall structure of dimeric tobacco 14-3-3 complexed to cotylenin A and the H^+-ATPase phosphopeptide QSYpTV. (a) Structure of cotylenin A. (b) Ribbon plot of the 14-3-3 dimer (monomers colored sand and brown) binding two molecules of the H^+-ATPase phosphopeptide (light blue sticks) and cotylenin A (yellow sticks). Each monomer of the anti-parallel 14-3-3 dimer comprises an amphipathic groove that accommodates the phosphopeptide as well as the cotylenin A molecule.

Figure 2.
Fig. 2. Binding of the H^+-ATPase phosphopeptide QSYpTV and cotylenin A to the amphipathic groove of 14-3-3. (a) Cotylenin A (yellow, sticks and semi-transparent surface) and the H^+-ATPase phosphopeptide QSYpTV (light blue, sticks and semi-transparent surface) are occupying the entire length of the amphipathic groove of 14-3-3 (sand surface), the extreme C-terminal Val956 of the peptide displays a hydrophobic contact to the tricarbon cycle of the cotylenin molecule. (b) Stereo view of the electron density for cotylenin A bound to 14-3-3 and the C-terminal tail of the H^+-ATPase peptide (QSYpTV-COOH). The peptide and cotylenin A are drawn in ball-and-stick mode, 14-3-3 is displayed as a ribbon (color coding as in a). An omit electron density map of cotylenin A (contoured at 3 σ) is shown in black. (c) Stereo view of a structural overlay of the position of the diterpene molecules and the H^+-ATPase phosphopeptide in the 14-3-3 complex structure with fusicoccin A (blue and magenta, respectively, PDB code 1O9F) and with cotylenin A (yellow and cyan, respectively).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 386, 913-919) copyright 2009.

Figures were selected by an automated process.