8F9D

Compound 21 bound to procaspase-6

8F9D の概要

• エントリーDOI: 10.2210/pdb8f9d/pdb
• 分子名称: Procaspase-6, 5-fluoro-2-({[(3M)-3-(1,2,4-oxadiazol-3-yl)pyridin-2-yl]amino}methyl)phenol, PENTAETHYLENE GLYCOL, ... (6 entities in total)
• 機能のキーワード: inhibitor, procaspase-6, protease, apoptosis, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 137466.19

構造登録者

Fan, P.,Zhao, Y.,Renslo, A.R.,Arkin, M.R. (登録日: 2022-11-23, 公開日: 2023-12-13, 最終更新日: 2024-06-26)

主引用文献

Togo, T.,Tram, L.,Denton, L.G.,ElHilali-Pollard, X.,Gu, J.,Jiang, J.,Liu, C.,Zhao, Y.,Zhao, Y.,Zheng, Y.,Zheng, Y.,Yang, J.,Fan, P.,Arkin, M.R.,Harma, H.,Sun, D.,Canan, S.S.,Wheeler, S.E.,Renslo, A.R.
Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6.
J.Med.Chem., 66:9784-9796, 2023

PubMed Abstract: Heteroaromatic stacking interactions are important in drug binding, supramolecular chemistry, and materials science, making protein-ligand model systems of these interactions of considerable interest. Here we studied 30 congeneric ligands that each present a distinct heteroarene for stacking between tyrosine residues at the dimer interface of procaspase-6. Complex X-ray crystal structures of 10 analogs showed that stacking geometries were well conserved, while high-accuracy computations showed that heteroarene stacking energy was well correlated with predicted overall ligand binding energies. Empirically determined values in this system thus provide a useful measure of heteroarene stacking with tyrosine. Stacking energies are discussed in the context of torsional strain, the number and positioning of heteroatoms, tautomeric state, and coaxial orientation of heteroarene in the stack. Overall, this study provides an extensive data set of empirical and high-level computed binding energies in a versatile new protein-ligand system amenable to studies of other intermolecular interactions.

PubMed: 37406165
DOI: 10.1021/acs.jmedchem.3c00590

実験手法

X-RAY DIFFRACTION (2.65 Å)