6yqi

Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with long-chain Fasudil-derivative N-[2-(propylamino)ethyl]isoquinoline-5-sulfonamide (soaked)

spinqualitylabelsall models 6yqi, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6yqi is a 2 chain structure with sequence from Cricetulus griseus and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.42Å Ligands: 6TV, SEP, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Two Methods, one Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.,Klebe G, Wienen-Schmidt B, Oebbeke M, Ngo K, Heine A ChemMedChem. 2020 Oct 8. doi: 10.1002/cmdc.202000565. PMID:33029876 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also CAMP-dependent protein kinase 3D structures

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