6yqk
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with a methylisoquinoline Fasudil-derivative (soaked)== |
| - | <StructureSection load='6yqk' size='340' side='right'caption='[[6yqk]]' scene=''> | + | <StructureSection load='6yqk' size='340' side='right'caption='[[6yqk]], [[Resolution|resolution]] 1.67Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6yqk]] 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=6YQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YQK FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7KB:5-(1,4-diazepan-1-ylsulfonyl)-4-methyl-isoquinoline'>7KB</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=6yqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yqk OCA], [https://pdbe.org/6yqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yqk RCSB], [https://www.ebi.ac.uk/pdbsum/6yqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yqk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/IPKA_MOUSE IPKA_MOUSE] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains. | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6yqk" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Cricetulus griseus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Heine A]] | ||
| + | [[Category: Klebe G]] | ||
| + | [[Category: Oebbeke M]] | ||
| + | [[Category: Wienen-Schmidt B]] | ||
Revision as of 13:33, 24 January 2024
Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with a methylisoquinoline Fasudil-derivative (soaked)
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