6YNC

Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with the methylated Fasudil-derived fragment N-methylisoquinoline-5-sulfonamide (soaked)

6YNC の概要

• エントリーDOI: 10.2210/pdb6ync/pdb
• 分子名称: cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase inhibitor alpha, ~{N}-methylisoquinoline-5-sulfonamide, ... (4 entities in total)
• 機能のキーワード: phosphotransferase, signalling pathways, glycogen metabolism, serine/threonine kinase, transferase
• 由来する生物種: Cricetulus griseus (Chinese hamster); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43409.33

構造登録者

Oebbeke, M.,Wienen-Schmidt, B.,Heine, A.,Klebe, G. (登録日: 2020-04-13, 公開日: 2020-10-14, 最終更新日: 2024-10-09)

主引用文献

Wienen-Schmidt, B.,Oebbeke, M.,Ngo, K.,Heine, A.,Klebe, G.
Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.
Chemmedchem, 16:292-300, 2021

PubMed Abstract: In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein-ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein-ligand complexes.

PubMed: 33029876
DOI: 10.1002/cmdc.202000565

実験手法

X-RAY DIFFRACTION (1.4 Å)