Cited by 9414-3-3 protein interactionsProtein Interaction Studies and Fluorescence AnalysisCrystal structures of chemical compounds

A Structural Rationale for Selective Stabilization of Anti-tumor Interactions of 14-3-3 proteins by Cotylenin A

Ottmann, Christian, Weyand, Michael, Sassa, Takeshi, Inoue, Takatsugu, Kato, Nobuo, Wittinghofer, Alfred, Oecking, Claudia·2009·Journal of Molecular Biology

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.

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Crossref · 10.1016/j.jmb.2009.01.005

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  • Fusicoccanes induce targeted stabilization between 14-3-3 proteins and part of their interactome.

    “Often called ''chemical stabilizers'', fusicoccanes (e.g., fusicoccin A, cotylenin A) induce the targeted stabilization between the 14-3-3 proteins and part of its interactome (Fig. 4).[83][84][85]”

    From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [84]

  • Cotylenin diterpenes form interfaces between the 14-3-3 protein family and a variety of interacting partners.

    “The cotylenin diterpenes form interfaces between the 14-3-3 protein family and a variety of interacting partners 8.”

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Authors
Ottmann, C., Weyand, M., Sassa, T., Inoue, T., Kato, N., Wittinghofer, A., & Oecking, C.
Affiliations
  • Max Planck Society (DE)
  • Yamagata University (JP)
  • The Institute of Scientific and Industrial Research, The University of Osaka (JP)
  • Max Planck Institute of Molecular Physiology (DE)
  • University of Tübingen (DE)
Corresponding author
  • Ottmann, Christian
  • Oecking, Claudia
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2009-03
Volume
386
Issue
4
Pages
913-919
ISSN
0022-2836 (ISSN-L)
OpenAlex
W2039369286
Cited by
94
References
35
Citations by year
2026: 1 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 1 · 2015: 8 · 2014: 7 · 2013: 3 · 2012: 7
FWCI
2.55
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • TU/e Research Portal (publishedVersion)
  • TU/e Research Portal (submittedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Physical Sciences › Chemistry › Inorganic Chemistry › Crystal structures of chemical compounds
Keywords
14-3-3 proteins, fusicoccin A, protein-protein interaction, anticancer activity, crystal structure, structure-activity relationship, fungal metabolites
MeSH terms
Amino Acid Sequence, Antineoplastic Agents, Calorimetry, Diterpenes, Glycosides, Proton-Translocating ATPases, Humans, Models, Molecular, Molecular Sequence Data, Phosphopeptides, Protein Binding, Structure-Activity Relationship, Nicotiana, Protein Structure, Secondary, Crystallography, X-Ray, Amino Acid Motifs, 14-3-3 Proteins, Protein Multimerization, Protein Stability

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