3plq: Difference between revisions

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-{{Seed}}
-[[Image:3plq.jpg|left|200px]]
-<!--
+==Crystal structure of PKA type I regulatory subunit bound with Rp-8-Br-cAMPS==
-The line below this paragraph, containing "STRUCTURE_3plq", creates the "Structure Box" on the page.
+<StructureSection load='3plq' size='340' side='right'caption='[[3plq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3plq]] 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=3PLQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PLQ FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RP2:(2R,4AR,6R,7R,7AS)-6-(6-AMINO-8-BROMO-9H-PURIN-9-YL)TETRAHYDRO-4H-FURO[3,2-D][1,3,2]DIOXAPHOSPHININE-2,7-DIOL+2-SULFIDE'>RP2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3plq|  PDB=3plq  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3plq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3plq OCA], [https://pdbe.org/3plq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3plq RCSB], [https://www.ebi.ac.uk/pdbsum/3plq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3plq ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KAP0_BOVIN KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
+<div style="background-color:#fffaf0;">
+== 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.
-===Crystal structure of PKA type I regulatory subunit bound with Rp-8-Br-cAMPS===
+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<ref>PMID:21081668</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3plq" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-PLQ is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PLQ OCA].
+*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
-[[Category: Swaminathan, K.]]
+[[Category: Large Structures]]
-[[Category: Pka]]
+[[Category: Swaminathan K]]
-[[Category: Transferase inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec  1 11:35:53 2010''