3iia

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[[Image:3iia.png|left|200px]]
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==Crystal structure of apo (91-244) RIa subunit of cAMP-dependent protein kinase==
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<StructureSection load='3iia' size='340' side='right' caption='[[3iia]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3iia]] 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=3IIA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IIA FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rgs|1rgs]], [[1rl3|1rl3]], [[1ne4|1ne4]], [[1ne6|1ne6]], [[3fhi|3fhi]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAR1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3iia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iia OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3iia RCSB], [http://www.ebi.ac.uk/pdbsum/3iia PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ii/3iia_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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<!--
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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>
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The line below this paragraph, containing "STRUCTURE_3iia", creates the "Structure Box" on the page.
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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or leave the SCENE parameter empty for the default display.
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-->
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{{STRUCTURE_3iia| PDB=3iia | SCENE= }}
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===Crystal structure of apo (91-244) RIa subunit of cAMP-dependent protein kinase===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<!--
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<references/>
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The line below this paragraph, {{ABSTRACT_PUBMED_21081668}}, adds the Publication Abstract to the page
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__TOC__
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(as it appears on PubMed at http://www.pubmed.gov), where 21081668 is the PubMed ID number.
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</StructureSection>
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-->
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{{ABSTRACT_PUBMED_21081668}}
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==About this Structure==
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[[3iia]] 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=3IIA OCA].
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==See Also==
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*[[CAMP-dependent protein kinase]]
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==Reference==
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<ref group="xtra">PMID:021081668</ref><references group="xtra"/>
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Kim, C.]]
[[Category: Kim, C.]]

Revision as of 09:39, 21 May 2014

Crystal structure of apo (91-244) RIa subunit of cAMP-dependent protein kinase

3iia, resolution 2.70Å

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