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| | <StructureSection load='3iia' size='340' side='right'caption='[[3iia]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='3iia' size='340' side='right'caption='[[3iia]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3iia]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IIA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3iia]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IIA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1rgs|1rgs]], [[1rl3|1rl3]], [[1ne4|1ne4]], [[1ne6|1ne6]], [[3fhi|3fhi]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAR1A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3iia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iia OCA], [https://pdbe.org/3iia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iia RCSB], [https://www.ebi.ac.uk/pdbsum/3iia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iia ProSAT]</span></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=3iia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iia OCA], [https://pdbe.org/3iia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iia RCSB], [https://www.ebi.ac.uk/pdbsum/3iia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iia ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KAP0_BOVIN KAP0_BOVIN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
| + | [https://www.uniprot.org/uniprot/KAP0_BOVIN KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kim, C]] | + | [[Category: Kim C]] |
| - | [[Category: Kornev, A P]] | + | [[Category: Kornev AP]] |
| - | [[Category: Sjoberg, T J]] | + | [[Category: Sjoberg TJ]] |
| - | [[Category: Taylor, S S]] | + | [[Category: Taylor SS]] |
| - | [[Category: Camp]]
| + | |
| - | [[Category: Camp-binding]]
| + | |
| - | [[Category: Cyclic amp]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein kinase some]]
| + | |
| - | [[Category: Ria subunit]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KAP0_BOVIN Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The regulatory (R) subunit of Protein Kinase A (PKA) serves to modulate the activity of PKA in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, endpoint cAMP-bound 'B' and C-subunit-bound 'H'-conformations. Here we report X-ray crystallography showing surprisingly that the antagonist Rp-cAMPS-bound R-subunit crystallized in the 'H' conformation which was previously assumed to be induced only by C-subunit-binding. Interestingly the apo R-subunit crystallized in the 'B' conformation similar to the cAMP-bound protein. However amide hydrogen exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Ion mobility mass spectrometry reveals the apo R-subunit is an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies which explained the basis for cAMP action through 'induced fit', our results support a conformational selection model, where the ligand-free apo form of the R-subunit exists as an ensemble of both 'B' and 'H' conformations. While cAMP preferentially binds the 'B' conformation, Rp-cAMPS preferentially binds the 'H' conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from 'H' to 'B' forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially 'select' inactive conformations of target proteins by satisfying all 'binding' constraints alone without inducing conformational changes necessary for activation.
Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: Conformational selection highlights a new concept in allosteric inhibitor design.,Badireddy S, Yunfeng G, Ritchie M, Akamine P, Wu J, Kim CW, Taylor SS, Qingsong L, Swaminathan K, Anand GS Mol Cell Proteomics. 2010 Nov 16. PMID:21081668[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Badireddy S, Yunfeng G, Ritchie M, Akamine P, Wu J, Kim CW, Taylor SS, Qingsong L, Swaminathan K, Anand GS. Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: Conformational selection highlights a new concept in allosteric inhibitor design. Mol Cell Proteomics. 2010 Nov 16. PMID:21081668 doi:10.1074/mcp.M110.004390
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