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5n33
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==cAMP-dependent Protein Kinase A from Cricetulus griseus in complex with fragment like molecule 3-amino-5-(trifluoromethyl)-1H-pyridin-2-one== | |
| + | <StructureSection load='5n33' size='340' side='right'caption='[[5n33]], [[Resolution|resolution]] 1.43Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5n33]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N33 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]] 1.434Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8JW:3-azanyl-5-(trifluoromethyl)-1~{H}-pyridin-2-one'>8JW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=5n33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n33 OCA], [https://pdbe.org/5n33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n33 RCSB], [https://www.ebi.ac.uk/pdbsum/5n33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n33 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/G3HK48_CRIGR G3HK48_CRIGR] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Medicinal-chemistry optimization follows strategies replacing functional groups and attaching larger substituents at a promising lead scaffold. Well-established bioisosterism rules are considered, however, it is difficult to estimate whether the introduced modifications really match the required properties at a binding site. The electron density distribution and pKa values are modulated influencing protonation states and bioavailability. Considering the adjacent H-bond donor/acceptor pattern of the hinge binding motif in a kinase, we studied by crystallography a set of fragments to map the required interaction pattern. Unexpectedly, benzoic acid and benzamidine, decorated with the correct substituents, are totally bioisosteric just as carboxamide and phenolic OH. A mono-dentate pyridine nitrogen out-performs bi-dentate functionalities. The importance of correctly designing pKa values of attached functional groups by additional substituents at the parent scaffold is rendered prominent. | ||
| - | + | Fragment Binding to Kinase Hinge: If Charge Distribution and Local pKa Shifts Mislead Popular Bioisosterism Concepts.,Oebbeke M, Siefker C, Wagner B, Heine A, Klebe G Angew Chem Int Ed Engl. 2020 Oct 6. doi: 10.1002/anie.202011295. PMID:33021032<ref>PMID:33021032</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Heine | + | <div class="pdbe-citations 5n33" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==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: Heine A]] | ||
| + | [[Category: Klebe G]] | ||
| + | [[Category: Siefker C]] | ||
Current revision
cAMP-dependent Protein Kinase A from Cricetulus griseus in complex with fragment like molecule 3-amino-5-(trifluoromethyl)-1H-pyridin-2-one
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