View source for 6yqi


==Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with long-chain Fasudil-derivative N-[2-(propylamino)ethyl]isoquinoline-5-sulfonamide (soaked)==
<StructureSection load='6yqi' size='340' side='right'caption='[[6yqi]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6yqi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YQI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.42&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6TV:~{N}-[2-(propylamino)ethyl]isoquinoline-5-sulfonamide'>6TV</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6yqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yqi OCA], [https://pdbe.org/6yqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yqi RCSB], [https://www.ebi.ac.uk/pdbsum/6yqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yqi ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:33029876</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yqi" style="background-color:#fffaf0;"></div>

==See Also==
*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cricetulus griseus]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Heine A]]
[[Category: Klebe G]]
[[Category: Oebbeke M]]
[[Category: Wienen-Schmidt B]]