Targeting a Cryptic Pocket in a Protein–Protein Contact by Disulfide-Induced Rupture of a Homodimeric Interface

Autor: Xiulan Xie, Gerhard Klebe, Andreas Heine, Felix Terwesten, Vitalii A. Palchykov, Alexander Metz, T X Phong Nguyen, D. Nguyen, Klaus Reuter, S. Jakobi

Publikováno v: ACS Chemical Biology. 16:1090-1098

Interference with protein-protein interfaces represents an attractive as well as challenging option for therapeutic intervention and drug design. The enzyme tRNA-guanine transglycosylase, a target to fight Shigellosis, is only functional as a homodim

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da7cf0fee57befe9e6e3eb5aef7e764f
https://doi.org/10.1021/acschembio.1c00296

Price for Opening the Transient Specificity Pocket in Human Aldose Reductase upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis

Autor: Ewa Pol, Andreas Heine, Tobias Wulsdorf, C. Rechlin, Veronica Fridh, Philipp M. Toth, Wibke E. Diederich, Frithjof Martin Scheer, Felix Terwesten, Gerhard Klebe

Publikováno v: ACS chemical biology. 12(5)

Insights into the thermodynamic and kinetic signature of the transient opening of a protein-binding pocket resulting from accommodation of suitable substituents attached to a given parent ligand scaffold are presented. As a target, we selected human

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fda569ee51f070d1ea3f91839291bbbb
https://pubmed.ncbi.nlm.nih.gov/28287700

Identification of a novel polyfluorinated compound as a lead to inhibit the human enzymes aldose reductase and AKR1B10: structure determination of both ternary complexes and implications for drug design

Autor: Francesc X. Ruiz, Michael Betz, Felix Terwesten, Jesús Ángel de la Fuente, Alberto Podjarny, Alexandra Cousido-Siah, Xavier Parés, Sonia Manzanaro, Sergio Porté, Gerhard Klebe, María Jesús Martín, Angel R. de Lera, Jaume Farrés, Andre Mitschler

Publikováno v: Recercat: Dipósit de la Recerca de Catalunya
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Recercat. Dipósit de la Recerca de Catalunya
instname

Aldo-keto reductases (AKRs) are mostly monomeric enzymes which fold into a highly conserved (α/β)8barrel, while their substrate specificity and inhibitor selectivity are determined by interaction with residues located in three highly variable exter

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83ff6d8cb5a0cec41a9c441acfd8e49a
https://doi.org/10.1107/s1399004713033452

Ligand binding stepwise disrupts water network in thrombin: Enthalpic and entropic changes reveal classical hydrophobic effect

Autor: A. Biela, Felix Terwesten, Torsten Steinmetzer, Gerhard Klebe, Frank Sielaff, Andreas Heine

Publikováno v: J. Med. Chem., 55 (2012) 6094-6110.

Well-ordered water molecules are displaced from thrombin's hydrophobic S3/4-pocket by P3-varied ligands (Gly, d-Ala, d-Val, d-Leu to d-Cha with increased hydrophobicity and steric requirement). Two series with 2-(aminomethyl)-5-chlorobenzylamide and

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e7cb785fb7f9567a25dd6748fcdb1859