Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction

被引：2

作者：

Andlovic, Blaz ^{[1
,2
,3
]}

Valenti, Dario ^{[2
,3
,4
]}

Centorrino, Federica ^{[2
,3
]}

Picarazzi, Francesca ^{[5
]}

Hristeva, Stanimira ^{[4
]}

Hiltmann, Malgorzata ^{[1
]}

Wolf, Alexander ^{[1
]}

Cantrelle, Francois-Xavier ^{[6
,7
]}

Mori, Mattia ^{[5
]}

Landrieu, Isabelle ^{[6
,7
]}

Levy, Laura M. ^{[4
]}

Klebl, Bert ^{[1
]}

Tzalis, Dimitrios ^{[4
]}

Genski, Thorsten ^{[4
]}

Eickhoff, Jan ^{[1
]}

Ottmann, Christian ^{[2
,3
]}

机构：

[1] Lead Discovery Ctr GmbH, D-44227 Dortmund, Germany

[2] Eindhoven Univ Technol, Dept Biomed Engn, Lab Chem Biol, NL-5612 AZ Eindhoven, Netherlands

[3] Eindhoven Univ Technol, Inst Complex Mol Syst, NL-5612 AZ Eindhoven, Netherlands

[4] Taros Chem GmbH & Co KG, D-44227 Dortmund, Germany

[5] Univ Siena, Dept Biotechnol Chem & Pharm, I-53100 Siena, Italy

[6] Univ Lille, CNRS EMR9002, Integrat Struct Biol, F-59000 Lille, France

[7] Univ Lille, Inst Pasteur Lille, INSERM, RID AGE Risk Factors & Mol Determinants Aging Rela, F-59000 Lille, France

来源：

BIOCHEMISTRY | 2024年 / 63卷 / 17期

基金：

欧盟地平线“2020”;

关键词：

SMALL-MOLECULE STABILIZATION; LIGAND-BINDING; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; HIPPO PATHWAY; DISCOVERY; PHOSPHORYLATION; INHIBITOR; RECEPTOR; TARGETS;

D O I：

10.1021/acs.biochem.4c00248

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The identification of chemical starting points for the development of molecular glues is challenging. Here, we employed fragment screening and identified an allosteric stabilizer of the complex between 14-3-3 and a TAZ-derived peptide. The fragment binds preferentially to the 14-3-3/TAZ peptide complex and shows moderate stabilization in differential scanning fluorimetry and microscale thermophoresis. The binding site of the fragment was predicted by molecular dynamics calculations to be distant from the 14-3-3/TAZ peptide interface, located between helices 8 and 9 of the 14-3-3 protein. This site was confirmed by nuclear magnetic resonance and X-ray protein crystallography, revealing the first example of an allosteric stabilizer for 14-3-3 protein-protein interactions.

引用

页码：2196 / 2206

页数：11

共 50 条

[31] Fragment-based quantum mechanical calculation of protein-protein binding affinities
Wang, Yaqian
Liu, Jinfeng
Li, Jinjin
He, Xiao
JOURNAL OF COMPUTATIONAL CHEMISTRY, 2018, 39 (21) : 1617 - 1628
[32] Interaction of the parathyroid hormone receptor with the 14-3-3 protein
Tazawa, H
Takahashi, S
Zilliacus, J
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2003, 1620 (1-3): : 32 - 38
[33] Targeting 14-3-3 adaptor protein-protein interactions to stimulate central nervous system repair
Kaplan, Andrew
Fournier, Alyson E.
NEURAL REGENERATION RESEARCH, 2017, 12 (07) : 1040 - 1043
[34] Molecular basis for the recognition of steroidogenic acute regulatory protein by the 14-3-3 protein family
Tugaeva, Kristina V.
Titterington, James
Sotnikov, Dmitriy V.
Maksimov, Eugene G.
Antson, Alfred A.
Sluchanko, Nikolai N.
FEBS JOURNAL, 2020, 287 (18) : 3944 - 3966
[35] Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions
Cau, Ylenia
Fiorillo, Annarita
Mori, Mattia
Ilari, Andrea
Botta, Maurizo
Lalle, Marco
JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2015, 55 (12) : 2611 - 2622
[36] Structural basis of 14-3-3 protein functions
Obsil, Tomas
Obsilova, Veronika
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2011, 22 (07) : 663 - 672
[37] Fragment-based drug discovery supports drugging 'undruggable' protein-protein interactions
Wang, Zhi-Zheng
Shi, Xing-Xing
Huang, Guang-Yi
Hao, Ge-Fei
Yang, Guang-Fu
TRENDS IN BIOCHEMICAL SCIENCES, 2023, 48 (06) : 539 - 552
[38] Fragment-Based Stabilizers of Protein-Protein Interactions through Imine-Based Tethering
Wolter, Madita
Valenti, Dario
Cossar, Peter J.
Levy, Laura M.
Hristeva, Stanimira
Genski, Thorsten
Hoffmann, Torsten
Brunsveld, Luc
Tzalis, Dimitrios
Ottmann, Christian
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2020, 59 (48) : 21520 - 21524
[39] Effect of phosphorylation on interaction of human tau protein with 14-3-3ζ
Sluchanko, Nikolai N.
Seit-Nebi, Alim S.
Gusev, Nikolai B.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 379 (04) : 990 - 994
[40] Design, expression, purification and crystallization of human 14-3-3ζ. protein chimera with phosphopeptide from proapoptotic protein BAD
Tugaeva, Kristina, V
Remeeva, Alina
Gushchin, Ivan
Cooley, Richard B.
Sluchanko, Nikolai N.
PROTEIN EXPRESSION AND PURIFICATION, 2020, 175

← 1 2 3 4 5 →